Mesenchymal stem cells(MSCs)are stem/progenitor cells capable of self-renewal and differentiation into osteoblasts,chondrocytes and adipocytes.The transformation of multipotent MSCs to adipocytes mainly involves two s...Mesenchymal stem cells(MSCs)are stem/progenitor cells capable of self-renewal and differentiation into osteoblasts,chondrocytes and adipocytes.The transformation of multipotent MSCs to adipocytes mainly involves two subsequent steps from MSCs to preadipocytes and further preadipocytes into adipocytes,in which the process MSCs are precisely controlled to commit to the adipogenic lineage and then mature into adipocytes.Previous studies have shown that the master transcription factors C/enhancer-binding protein alpha and peroxisome proliferation activator receptor gamma play vital roles in adipogenesis.However,the mechanism underlying the adipogenic differentiation of MSCs is not fully understood.Here,the current knowledge of adipogenic differentiation in MSCs is reviewed,focusing on signaling pathways,noncoding RNAs and epigenetic effects on DNA methylation and acetylation during MSC differentiation.Finally,the relationship between maladipogenic differentiation and diseases is briefly discussed.We hope that this review can broaden and deepen our understanding of how MSCs turn into adipocytes.展开更多
Objective:Polyploid giant cancer cells(PGCCs)with daughter cells express epithelial–mesenchymal transition(EMT)-associated proteins.Highly malignant tumor cells with EMT properties can transdifferentiate into mature ...Objective:Polyploid giant cancer cells(PGCCs)with daughter cells express epithelial–mesenchymal transition(EMT)-associated proteins.Highly malignant tumor cells with EMT properties can transdifferentiate into mature tumor cells.In this study,we elucidated the potential for,and underlying mechanism of,adipogenic differentiation of PGCCs with daughter cells(PDCs).Methods:Cobalt chloride was used to induce PGCC formation in HEY(wild-type P53)and MDA-MB-231(mutant P53)cells;these cells were then cultured in adipogenic differentiation medium.Oil red O staining was used to confirm adipogenic differentiation,and the cell cycle was detected with flow cytometry.The expression of adipogenic differentiation-associated proteins and P300 histone acetyltransferase activity were compared before and after adipogenic differentiation.Animal xenograft models were used to confirm the adipogenic differentiation of PDCs.Results:PDCs transdifferentiated into functional adipocytes.Two different cell cycle distributions were observed in PDCs after adipogenic differentiation.The expression levels of PPARγ,Ace-PPARγ,and Ace-P53 were higher in PDCs after adipogenic differentiation than in cells before adipogenic differentiation.Ace-PPARγand FABP4 expression increased in HEY cells and decreased in MDA-MB-231 PDCs after p53 knockdown.A485 treatment increased Ace-P53,Ace-PPARγ,and FABP4 expression in HEY PDCs by inhibiting SUMOylation of P53.In MDA-MB-231 PDCs,A485 treatment decreased Ace-P53,Ace-PPARγ,and FABP4 expression.Animal experiments also confirmed the adipogenic differentiation of PDCs.Conclusions:Acetylation of P53 and PPARγplays an important role in the adipogenic differentiation of PDCs.展开更多
YAP（yes-associated protein） is a transcriptional factor that is negatively regulated by Hippo pathway, a conserved pathway for the development and size control of multiple organs. The exact function of YAP in bone h...YAP（yes-associated protein） is a transcriptional factor that is negatively regulated by Hippo pathway, a conserved pathway for the development and size control of multiple organs. The exact function of YAP in bone homeostasis remains controversial. Here we provide evidence for YAP＇s function in promoting osteogenesis, suppressing adipogenesis, and thus maintaining bone homeostasis.YAP is selectively expressed in osteoblast（OB）-lineage cells. Conditionally knocking out Yap in the OB lineage in mice reduces cell proliferation and OB differentiation and increases adipocyte formation, resulting in a trabecular bone loss. Mechanistically, YAP interacts with β-catenin and is necessary for maintenance of nuclear β-catenin level and Wnt/β-catenin signaling. Expression of β-catenin in YAP-deficient BMSCs（bone marrow stromal cells） diminishes the osteogenesis deficit. These results thus identify YAP-β-catenin as an important pathway for osteogenesis during adult bone remodeling and uncover a mechanism underlying YAP regulation of bone homeostasis.展开更多
AIM: To study the metabolic profile of human umbilical mesenchymal stem cells (HUMSC) and adipogenic differentiation by nuclear magnetic resonance (NMR) spectroscopy.
Obesity is a major human health problem associated with various diseases, including cardiac injury and type 2 diabetes. Trapa japonica Flerov (TJF) has been used in traditional oriental medicine to treat diabetes. In ...Obesity is a major human health problem associated with various diseases, including cardiac injury and type 2 diabetes. Trapa japonica Flerov (TJF) has been used in traditional oriental medicine to treat diabetes. In this study, we evaluated the inhibitory effect of and the mechanism underlying the effect of TJF extract on adipogenesis in 3T3-L1 cells. The effects of TJF extract on cell viability were analyzed using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, and the anti-adipogenic effect was measured by oil red O staining. The expression of peroxisomal proliferator activated receptor (PPAR)γ, CCAAT/enhancer-binding protein-α (C/EBP)α, adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), adiponectin, and fatty acid binding protein (FABP)4 involved in adipogenesis was determined by western blot analysis. TJF extract effectively inhibited lipid accumulation and the expression of PPARγ and C/EBPα in 3T3-L1 cells. TJF also increased the phosphorylation of AMPK and ACC, and decreased the expression of adiponectin and FABP4. These results indicate that TJF extract exerts its anti-obesity effect through the downregulation of adipogenic transcription factors and adipogenic marker genes.展开更多
Objective:To determine the effect of Salvianolic acid B (Sal B) on glucose and lipid metabolism in mice with high-fat diet (HFD)-induced obesity,and to investigate the underlying mechanisms by measuring the expression...Objective:To determine the effect of Salvianolic acid B (Sal B) on glucose and lipid metabolism in mice with high-fat diet (HFD)-induced obesity,and to investigate the underlying mechanisms by measuring the expression levels of key adipogenic transcription factors.Methods:Six-week-old C57BL/6J male mice were fed for 12 weeks with a HFD to induce obesity or a standard diet to serve as normal controls.A mean body weight increase of more than 20% after these 12 weeks was used as the criteria for obesity.HFD-fed obese mice then received a supplement of Sal B (100 mg/kg body weight/day),metformin (75 mg/kg body weight/day) or water (an equivalent volume;served as model controls) by oral gavage for an additional 8 weeks,and the normal controls received water (an equivalent volume) by oral gavage for the same period.Results:Sal B significantly reduced body weight gain (P <.05) without influencing food intake in HFD-fed obese mice relative to model controls.Sal B also reduced the body fat mass of the obese mice relative to model controls in a time-dependent manner (P <.05).Sal B significantly decreased the serum concentrations of low-density lipoprotein cholesterol,total cholesterol,triglyceride and free fatty acids by 25.5%,20.2%,20.6% and 13.4%,respectively,and increased the concentration of high-density lipoprotein cholesterol by 50.1% relative to model controls.In addition,Sal B significantly lowered fasting glucose concentrations and improved insulin sensitivity relative to model controls (P <.05).Sal B acted by ameliorating the histopathological changes in both brown and white adipose tissues of obese mice.Moreover,in brown adipose tissue,Sal B up-regulated the mRNA and protein expression of PPARγ and c/EBPα,and the protein expression of PPARα and SREBP-1 (P <.05).In white adipose tissue,Sal B down-regulated the mRNA expression of PPARγ and c/EBPα,and decreased the protein expression of PPARγ and SREBP-1(P <.05).Conclusjons:The results suggest that Sal B can reduce body weight gain and regulate glucose and lipid metabolism in mice with diet-induced obesity by regulating adipogenic transcription factors in their adipose tissues.展开更多
BACKGROUND Osteoporosis(OP)has become a major public health problem worldwide.Most OP treatments are based on the inhibition of bone resorption,and it is necessary to identify additional treatments aimed at enhancing ...BACKGROUND Osteoporosis(OP)has become a major public health problem worldwide.Most OP treatments are based on the inhibition of bone resorption,and it is necessary to identify additional treatments aimed at enhancing osteogenesis.In the bone marrow(BM)niche,bone mesenchymal stem cells(BMSCs)are exposed to a hypoxic environment.Recently,a few studies have demonstrated that hypoxiainducible factor 2alpha(HIF-2α)is involved in BMSC osteogenic differentiation,but the molecular mechanism involved has not been determined.AIM To investigate the effect of HIF-2αon the osteogenic and adipogenic differentiation of BMSCs and the hematopoietic function of hematopoietic stem cells(HSCs)in the BM niche on the progression of OP.METHODS Mice with BMSC-specific HIF-2αknockout(Prx1-Cre;Hif-2αfl/fl mice)were used for in vivo experiments.Bone quantification was performed on mice of two genotypes with three interventions:Bilateral ovariectomy,semilethal irradiation,and dexamethasone treatment.Moreover,the hematopoietic function of HSCs in the BM niche was compared between the two mouse genotypes.In vitro,the HIF-2αagonist roxadustat and the HIF-2αinhibitor PT2399 were used to investigate the function of HIF-2αin BMSC osteogenic and adipogenic differentiation.Finally,we investigated the effect of HIF-2αon BMSCs via treatment with the mechanistic target of rapamycin(mTOR)agonist MHY1485 and the mTOR inhibitor rapamycin.RESULTS The quantitative index determined by microcomputed tomography indicated that the femoral bone density of Prx1-Cre;Hif-2αfl/fl mice was lower than that of Hif-2αfl/fl mice under the three intervention conditions.In vitro,Hif-2αfl/fl mouse BMSCs were cultured and treated with the HIF-2αagonist roxadustat,and after 7 d of BMSC adipogenic differentiation,the oil red O staining intensity and mRNA expression levels of adipogenesis-related genes in BMSCs treated with roxadustat were decreased;in addition,after 14 d of osteogenic differentiation,BMSCs treated with roxadustat exhibited increased expression of osteogenesis-related genes.The opposite effects were shown for mouse BMSCs treated with the HIF-2αinhibitor PT2399.The mTOR inhibitor rapamycin was used to confirm that HIF-2αregulated BMSC osteogenic and adipogenic differentiation by inhibiting the mTOR pathway.Consequently,there was no significant difference in the hematopoietic function of HSCs between Prx1-Cre;Hif-2αfl/fl and Hif-2αfl/fl mice.CONCLUSION Our study showed that inhibition of HIF-2αdecreases bone mass by inhibiting the osteogenic differentiation and increasing the adipogenic differentiation of BMSCs through inhibition of mTOR signaling in the BM niche.展开更多
Background Steroids inhibit osteogenic differentiation and decrease bone formation while concomitantly inducing adipose deposition in osteocytes.This leads to the fatty degeneration and necrosis of bone cells commonly...Background Steroids inhibit osteogenic differentiation and decrease bone formation while concomitantly inducing adipose deposition in osteocytes.This leads to the fatty degeneration and necrosis of bone cells commonly seen in osteonecrosis of the femoral head.The peroxisome proliferator-activated receptor-γ （PPARγ） is an adipogenic transcription factor linked to the development of this disease and responsible for inducing adipogenesis over osteogenesis in bone marrow mesenchymal stem cells （BMSCs）.The aim of this study was to assess whether adipogenic differentiation could be suppressed,and thus osteogenic potential retained,by inhibiting PPARy expression in BMSCs.Methods Cells from the bone marrow of New Zealand rabbits were treated with 10-7 mol/L dexamethasone and infected with one of three small interference RNA （siRNA） adenovirus vectors （S1,S2,and S3） or non-targeting control siRNA （Con） and compared with dexamethasone-treated （model） and untreated （normal） cells.Cells were grown for 21 days and stained with Sudan Ⅲ for adipocyte formation.At various time points,cells were also assessed for changes in PPARγ,osteocalcin （OC）,Runx2,alkaline phosphatase （ALP） activity,and triglyceride （TG） content.Results Dexamethasone-treated model and control groups showed a significant increase in fatty acid-positive staining,which was inhibited in cells treated with PPARγ siRNA-treated,similar to normal untreated cells.All three siRNA groups significantly inhibited PPARγ mRNA and protein,adipocyte number,and TG content compared with the dexamethasonetreated model and control groups,matching that seen in normal cells.OC and Runx2 mRNA and protein,as well as ALP activity,were significantly higher in cells treated with siRNA against PPARγ,similar to that seen in the normal cells.These osteogenic markers were significantly lower in the dexamethasone-treated cell cultures.Conclusions The siRNA adenovirus vector targeting PPARγ can efficiently inhibit steroid-induced adipogenic differentiation in rabbit BMSCs and retain their osteogenic differentiation potential.展开更多
Porcine mesenchymal stem cells in postnatal muscle have been demonstrated to differentiate into adipocytes. This increases adipocyte number and lipid accumulation, and is thought to be the origin of intramuscular fat....Porcine mesenchymal stem cells in postnatal muscle have been demonstrated to differentiate into adipocytes. This increases adipocyte number and lipid accumulation, and is thought to be the origin of intramuscular fat. In this study, the effects of myostatin and arginine on adipogenic differentiation in mesenchymal stem cells derived from porcine muscle （pMDSCs） were investigated in vitro. Intracellular triglyceride levels were reduced by exogenous myostatin and increased by arginine supplementation or myostatin antibody （P〈0.01）. The inhibition of lipid accumulation by rnyostatin in pMDSCs was alleviated by arginine supplementation （P〈0.01）. Expression patterns of adipogenic transcription factors showed that exogenous myostatin suppressed PPAR72 and aP2 expression （P〈0.01）, while supplemental arginine or myostatin antibody promoted ADD1 expression （P〈0.01）. Furthermore, compared with the addition of either myostatin protein or antibody alone, ADD1 and PPARδ expression were promoted by the combination of arginine and myostatin （P〈0.01）, and arginine combined with myostatin antibody promoted the expression of ADD1, PPARδ, C/EBPα, PPARγ2 and LPL in pMDSCs （P〈0.05）. These results suggest that myostatin inhibits adipogenesis in pMDSCs, and that this can be alleviated by arginine supplementation, at least in part, through promoting ADD1 and PPARδ expression.展开更多
Extracellular matrix （ECM） plays a very important role in regulating cell function and fate. It is highly desirable to fabricate biomimetic models to investigate the role of ECM in stem cell differentiation. In this...Extracellular matrix （ECM） plays a very important role in regulating cell function and fate. It is highly desirable to fabricate biomimetic models to investigate the role of ECM in stem cell differentiation. In this study, arginine- glycine--aspartate （RGD）-modified gold nanoparticles （Au NPs） with tunable surface ligand density were prepared to mimic the ECM microenvironment. Their effect on osteogenic and adipogenic differentiation of human mesenchymal stem cells （MSCs） was investigated. The biomimetic Au NPs were taken up by MSCs in a ligand density-dependent manner. The biomimetic NPs with a high RGD density had an inhibitive effect on the alkaline phosphatase （ALP） activity, calcium deposition, and osteogenic marker gene expression of MSCs. Their effect on oil droplet formation and adipogenic marker gene expression was negative when RGD density was low, while their effect was promotive when RGD density was high. The biomimetic Au NPs regulated the osteogenic and adipogenic differentiation of MSCs mainly through affecting the focal adhesion and cytoskeleton. This study highlights the roles of biomimetic NPs on stem cell differentiation that could provide a meaningful strategy in fabricating functional biomaterials for tissue engineering and biomedical applications.展开更多
In order to elucidate the action of La3＋ on bone metabolism,effects of La3＋ on the osteogenic and adipogenic differentiation of pri-mary mouse bone marrow stromal cells（BMSCs） were studied by 3-（4,5-dimethylthiaz...In order to elucidate the action of La3＋ on bone metabolism,effects of La3＋ on the osteogenic and adipogenic differentiation of pri-mary mouse bone marrow stromal cells（BMSCs） were studied by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide（MTT） test,alkaline phosphatase（ALP） activity measurement,mineralized function,oil red O stain and measurement.The results showed that La3＋ pro-moted the proliferation of BMSCs except at 1×10-10 and 1×10-6 mol/L.The effect of La3＋ on the osteogenic differentiation depended on con-centrations at the 7th day,but the osteogenic differentiation was inhibited at any concentration at the 14th day.La3＋ promoted the formation of mineralized matrix nodules except at 1×10-8 and 1×10-5 mol/L.La3＋ inhibited adipogenic differentiation except at 1×10-10 and 1×10-7 mol/L at the 10th day,and inhibited adipogenic differentiation except at 1×10-9 mol/L at the 16th day.These findings suggested that La3＋ might have protective effect on bone at appropriate dose and time.This would be valuable for better understanding the mechanism of the effect of La3＋ on bone metabolism.展开更多
Mesenchymal stem cells(MSCs)are multi-potent cells that are able to differentiate and mature into various types of cells under a certain microenvironment for cell therapy and tissue regeneration.Scandium(Sc),an import...Mesenchymal stem cells(MSCs)are multi-potent cells that are able to differentiate and mature into various types of cells under a certain microenvironment for cell therapy and tissue regeneration.Scandium(Sc),an important rare earth element,recently has been intensively investigated in biomedical fields as well as industrial engineering,and chloride channels have been proven to be able to affect osteogenic differentiation.Thus,it is significant to investigate effects of ScCl_(3)on cell activities of MSCs.In this paper,rat bone MSCs(rBMSCs)were co-cultured with various concentrations of ScCl_(3)(1×10^(-8),1×10^(-6),and 1×10^(-4)mol/L)to evaluate their influence on cell proliferation as well as osteogenic and adipogenic differentiation in vitro.The results indicate that ScCl_(3)promotes the proliferation of rBMSCs initially,which is yet reduced upon ion accumulation.We used immunofluorescence staining,quantitative real time polymerase chain reactions,and assays measuring alkaline phosphatase activity,mineralized deposits,and intracytoplasmic lipids to reveal that rBMSCs treated with ScCl_(3)at concentrations of 1×10^(-8)-1×10^(-6)mol/L can enhance levels of osteogenic differentiation in a dosedependent manner and reduce adipogenic differentiation to a certain degree through Wnt/β-catenin signaling pathway.These results indicate that appropriate concentrations of ScCl_(3)can improve osteogenic differentiation in the lineage commitment of rBMSCs,and thus,promote bone remodeling.This study implies that ScCl_(3) possesses great potentials in the treatment of bone diseases and would provide new strategy of designing composites by SiCl3 doping for biomedical applications in the future.展开更多
The retinoblastoma gene product(pRb)is a chromatin-associated protein that can either suppress or promote activity of key regulators of tissue-specific differentiation.We found that twelve weeks after transfection of ...The retinoblastoma gene product(pRb)is a chromatin-associated protein that can either suppress or promote activity of key regulators of tissue-specific differentiation.We found that twelve weeks after transfection of the exogenous active(ΔB/X andΔр34)or inactive(ΔS/N)forms of RB into the 10T1/2 mesenchymal stem cells and clonal selection not a single cell line did contain exogenous RB,despite being G-418 resistant.However,the consequences of the transient production of exogenous RB had different effects on the cell fate.TheΔB/X andΔр34 cells transfected with active form of RB showed elevated levels of inducible adipocyte differentiation(AD).On the contrary,theΔS/N cells transfected with inactive RB mutant were insensitive to induction of AD associated with abolishing of expression of the PPARγ2.Additionally,the PPARγ2 promoter in undifferentiatedΔS/N cells was hypermethylated,but all except−60 position CpG became mostly demethylated after cells exposure to AD.We conclude that while transient expression of inactive exogenous RB induces long term epigenetic alterations that prevent adipogenesis,production of active exogenous RBs results in an AD-promoting epigenetic state.These results indicate that pRb is involved in the establishment of hereditary epigenetic memory at least by creating a methylation pattern of PPARγ2.展开更多
Imipramine （IM） has been widely used clinically for the treatment of mental disorders. Its actions on tissues or organs other than the nervous system also need to be understood for its proper clinical use. In this s...Imipramine （IM） has been widely used clinically for the treatment of mental disorders. Its actions on tissues or organs other than the nervous system also need to be understood for its proper clinical use. In this study, the effects of IM on adipogenic differentiation in both 3T3-L1 preadipocytes and mouse marrow stromal cells （MSCs） were investigated. The results showed that fewer adipocytic cells were developed from 3T3-L1 preadipocytes in the presence of 0.001 to 1 μmol/L of IM as compared to control. Similar inhibitory effect was also observed in mouse MSCs. The decrease in the formation of adipocytes was accompanied with significant down-regulation at mRNA expression of the early adipogenic transcription factor, peroxisome proliferator-activated receptor γ2 （PPARγ2）. Western blot analysis further revealed that the protein expression of PPARγ2 was reduced markedly in ceils treated with IM at concentrations of 0.01, 0.1 and 1 μmol/L, suggesting that the suppression on PPAR72 was involved in IM＇s inhibition on MSCs adipogenesis. Moreover, IM at the above concentrations could stimulate the mRNA expression of β2-adrenergic receptor （AR） and β3-AR, which implicated that the effect of IM on adipogenic differentiation was partially mediated by β-ARs. Our results demonstrated for the first time that the conventional antidepressive imipramine exerts accompanied inhibitory effect on adipocyte formation, which may have possible clinical implications.展开更多
Objective：The study was designed to investigate the molecular mechanism of quercitrin on osteogenic differentiation and adipogenic differentiation of r BMSCs.Methods：r BMSCs were harvested from SD rats,and determina...Objective：The study was designed to investigate the molecular mechanism of quercitrin on osteogenic differentiation and adipogenic differentiation of r BMSCs.Methods：r BMSCs were harvested from SD rats,and determination of alkaline phosphatase（ALP）activity,quantification of mineralization by Alizarin Red S staining,and the m RNA expression of osteogenic differentiation markers（Runx2,BMP-2,and OSX）by RT-PCR after r BMSCs stimulated by osteogenic induction with（0.1–10）μg/m L of quercitrin,quantification of Lipid droplet by Oil Red O staining and the m RNA expression of adipogenic differentiation marker（,and a P2）by RT-PCR after r BMSCs stimulated by adipogenic induction with（0.1-10）μg/m L of quercitrin.Results：Quercitrin can up-regulate the m RNA expression of osteogenic differentiation markers（Runx2,BMP-2,and OSX）and increase ALP activity and mineralization after osteogenic induction,on the other hand quercitrin can suppress the m RNA expression of adipogenic differentiation markers（,and a P2）and decrease lipid droplet after adipogenic induction.Conclusion：This study suggested that quercitrin not only stimulated osteogenic differentiation but also inhibited adipogenic differentiation of r BMSCs,which was associated with the up-regulation of Runx2,BMP-2,and OSX m RNA expression and the down-regulation of,and a P2 m RNA expression.展开更多
Aim:To evaluate the age-related effects on the adipogenic differentiation and proliferation potentials of human orbital adipose-derived stem cells(OASCs).Methods:Orbital adipose samples were harvested from the central...Aim:To evaluate the age-related effects on the adipogenic differentiation and proliferation potentials of human orbital adipose-derived stem cells(OASCs).Methods:Orbital adipose samples were harvested from the central fat compartment in the lower eyelids of 10 young and middle-aged patients during routine blepharoplasty surgery.After assessment of the morphological changes of adipocytes with aging,OASCs were isolated from the fat samples and expanded in vitro.Differences in the stem cell colony number(fibroblast colony-forming unit),growth rate and phenotype characterization(flow cytometry analysis)were evaluated.The ability of OASCs to differentiate into adipocytes was determined by oil red O staining and the mRNA expression level of peroxisome proliferator-activated receptorγ.Results:Fat cell size showed a decreasing trend with advancing age.Although no difference was found in the expression of cell surface markers,the colony number and proliferative rate of OASCs from middle-aged donors were significantly lower than those from the young donors.The adipogenic differentiation capacity of middle-aged OASCs was also reduced.These differences were statistically significant(P<0.001).Conclusion:The data showed that the progenitor cell number,proliferation capacity and adipogenic potential of OASCs decreased with aging,suggesting that using OASCs from elderly patients for therapeutic purposes might be restricted.展开更多
Over the past few decades,genetic selection and refined nutritional management have extensively been used to increase the growth rate and lean meat production of livestock.However,the rapid growth rates of modern bree...Over the past few decades,genetic selection and refined nutritional management have extensively been used to increase the growth rate and lean meat production of livestock.However,the rapid growth rates of modern breeds are often accompanied by a reduction in intramuscular fat deposition and increased occurrences of muscle abnor‑malities,impairing meat quality and processing functionality.Early stages of animal development set the long‑term growth trajectory of offspring.However,due to the seasonal reproductive cycles of ruminant livestock,gestational nutrient deficiencies caused by seasonal variations,frequent droughts,and unfavorable geological locations nega‑tively affect fetal development and their subsequent production efficiency and meat quality.Therefore,enrolling live‑stock in nutritional intervention strategies during gestation is effective for improving the body composition and meat quality of the offspring at harvest.These crucial early developmental stages include embryonic,fetal,and postnatal stages,which have stage‑specific effects on subsequent offspring development,body composition,and meat quality.This review summarizes contemporary research in the embryonic,fetal,and neonatal development,and the impacts of maternal nutrition on the early development and programming effects on the long‑term growth performance of livestock.Understanding the developmental and metabolic characteristics of skeletal muscle,adipose,and fibrotic tissues will facilitate the development of stage‑specific nutritional management strategies to optimize production efficiency and meat quality.展开更多
Bone marrow mesenchymal stem cells(BMSCs)are non-hematopoietic multipotent stem cells capable of differentiating into mature cells.Isoquercetin,an extract from natural sources,has shown promise as a potential treatmen...Bone marrow mesenchymal stem cells(BMSCs)are non-hematopoietic multipotent stem cells capable of differentiating into mature cells.Isoquercetin,an extract from natural sources,has shown promise as a potential treatment for osteoporosis.To investigate the therapeutic effects of isoquercetin on osteoporosis,bone marrow mesenchymal stem cells(BMSCs)were cultured in vitro,and osteogenesis or adipogenesis was induced in the presence of isoquercetin for 14 days.We evaluated cell viability,osteogenic and adipogenic differentiation,as well as mRNA expression levels of Runx2,Alpl,and OCN in osteoblasts,and mRNA expression levels of Pparγ,Fabp4,and Cebpαin adipocytes.The results showed that isoquercetin dose-dependently increased cell viability and promoted osteogenic differentiation,as evidenced by Alizarin Red and alkaline phosphatase staining and mRNA expression levels of Runx2,Alpl,and OCN in osteoblasts(P<0.05).In contrast,isoquercetin inhibited adipogenic differentiation and decreased the mRNA expres-sion levels of Pparγ,Fabp4,and Cebpαin adipocytes(P<0.05).In vivo,isoquercetin treatment increased bone quan-tity and density in an osteoporosis model mice group,as determined byμCT scanning and immunohistochemistry(P<0.05).These findings suggest that isoquercetin may have therapeutic potential for osteoporosis by promoting the proliferation and differentiation of BMSCs towards osteoblasts while inhibiting adipogenic differentiation.展开更多
The pathogenesis of myelodysplastic syndrome(MDS)may be related to the abnormal expression of microRNAs(miRNAs),which could influence the differentiation capacity of mesenchymal stem cells(MSCs)towards adipogenic and ...The pathogenesis of myelodysplastic syndrome(MDS)may be related to the abnormal expression of microRNAs(miRNAs),which could influence the differentiation capacity of mesenchymal stem cells(MSCs)towards adipogenic and osteogenic lineages.In this study,exosomes from bone marrow plasma were successfully extracted and identified.Assessment of miR-103-3p expression in exosomes isolated from BM in 34 MDS patients and 10 controls revealed its 0.52-fold downregulation in patients with MDS compared with controls(NOR)and was downregulated 0.55-fold in MDS-MSCs compared with NOR-MSCs.Transfection of MDS-MSCs with the miR-103-3p mimic improved osteogenic differentiation and decreased adipogenic differentiation in vitro,while inhibition of miR-103-3p showed the opposite results in NOR-MSCs.Thus,the expression of miR-103-3p decreases in MDS BM plasma and MDS-MSCs,significantly impacting MDS-MSCs differentiation.The miR-103-3p mimics may boost MDS-MSCs osteogenic differentiation while weakening lipid differentiation,thereby providing possible target for the treatment of MDS pathogenesis.展开更多
Background:Long non-coding RNAs(lncRNAs)are emerging key regulators involved in a variety of biological processes such as cell differentiation and development.The balance between myogenesis and adipogenesis is crucial...Background:Long non-coding RNAs(lncRNAs)are emerging key regulators involved in a variety of biological processes such as cell differentiation and development.The balance between myogenesis and adipogenesis is crucial for skeletal muscle homeostasis in humans and meat quality in farm animals.The present study aimed to reveal the global transcriptomic profiles of adipogenic(Adi-)and myogenic(Myo-)precursors derived from porcine skeletal muscle and identify lncRNAs involved in the modulation of myogenesis homeostasis in porcine skeletal muscle.Results:In this study,a total of 655 novel individual lncRNAs including differentially expressed 24 lncRNAs,and 755 differentially expressed mRNAs were identified(fold change≥2 or≤0.5 and adjusted P<0.05).Integrated results of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis accompanied by the variation of intracellular Ca2+concentration highlighted Lnc-ADAMTS9 involved in the modulation of myogenesis homeostasis in porcine skeletal muscle.Although Lnc-ADAMTS9 knock-down did not alter the mRNA expression of ADAMTS9,we demonstrated that Lnc-ADAMTS9 can promote myogenic proliferation and myogenic differentiation of myogenic precursors through inhibiting the ERK/MAPK signaling pathway.Conclusion:We deciphered a comprehensive catalog of mRNAs and lncRNAs that might be involved in the regulation of myogenesis and adipogenesis homeostasis in the skeletal muscle of pigs.The Lnc-ADAMTS9 exerts an essential role in myogenesis through the ERK signaling pathway.展开更多
基金Supported by the National Natural Science Foundation of China,No.82271843 and 31700779the Key Project supported by Medical Science and Technology Development Foundation,Nanjing Department of Health,No.ZKX20019the Natural Science Foundation of Jiangsu Province,No.BK20200137.
文摘Mesenchymal stem cells(MSCs)are stem/progenitor cells capable of self-renewal and differentiation into osteoblasts,chondrocytes and adipocytes.The transformation of multipotent MSCs to adipocytes mainly involves two subsequent steps from MSCs to preadipocytes and further preadipocytes into adipocytes,in which the process MSCs are precisely controlled to commit to the adipogenic lineage and then mature into adipocytes.Previous studies have shown that the master transcription factors C/enhancer-binding protein alpha and peroxisome proliferation activator receptor gamma play vital roles in adipogenesis.However,the mechanism underlying the adipogenic differentiation of MSCs is not fully understood.Here,the current knowledge of adipogenic differentiation in MSCs is reviewed,focusing on signaling pathways,noncoding RNAs and epigenetic effects on DNA methylation and acetylation during MSC differentiation.Finally,the relationship between maladipogenic differentiation and diseases is briefly discussed.We hope that this review can broaden and deepen our understanding of how MSCs turn into adipocytes.
基金supported partly by grants from the National Natural Science Foundation of China(Grant Nos.82173283 and 82103088)the Foundation of the Committee on Science and Technology of Tianjin(Grant No.20JCYBJC01230)。
文摘Objective:Polyploid giant cancer cells(PGCCs)with daughter cells express epithelial–mesenchymal transition(EMT)-associated proteins.Highly malignant tumor cells with EMT properties can transdifferentiate into mature tumor cells.In this study,we elucidated the potential for,and underlying mechanism of,adipogenic differentiation of PGCCs with daughter cells(PDCs).Methods:Cobalt chloride was used to induce PGCC formation in HEY(wild-type P53)and MDA-MB-231(mutant P53)cells;these cells were then cultured in adipogenic differentiation medium.Oil red O staining was used to confirm adipogenic differentiation,and the cell cycle was detected with flow cytometry.The expression of adipogenic differentiation-associated proteins and P300 histone acetyltransferase activity were compared before and after adipogenic differentiation.Animal xenograft models were used to confirm the adipogenic differentiation of PDCs.Results:PDCs transdifferentiated into functional adipocytes.Two different cell cycle distributions were observed in PDCs after adipogenic differentiation.The expression levels of PPARγ,Ace-PPARγ,and Ace-P53 were higher in PDCs after adipogenic differentiation than in cells before adipogenic differentiation.Ace-PPARγand FABP4 expression increased in HEY cells and decreased in MDA-MB-231 PDCs after p53 knockdown.A485 treatment increased Ace-P53,Ace-PPARγ,and FABP4 expression in HEY PDCs by inhibiting SUMOylation of P53.In MDA-MB-231 PDCs,A485 treatment decreased Ace-P53,Ace-PPARγ,and FABP4 expression.Animal experiments also confirmed the adipogenic differentiation of PDCs.Conclusions:Acetylation of P53 and PPARγplays an important role in the adipogenic differentiation of PDCs.
基金supported in part by grants from the National Institutes of Health(AG051773)and VA(BX000838)
文摘YAP（yes-associated protein） is a transcriptional factor that is negatively regulated by Hippo pathway, a conserved pathway for the development and size control of multiple organs. The exact function of YAP in bone homeostasis remains controversial. Here we provide evidence for YAP＇s function in promoting osteogenesis, suppressing adipogenesis, and thus maintaining bone homeostasis.YAP is selectively expressed in osteoblast（OB）-lineage cells. Conditionally knocking out Yap in the OB lineage in mice reduces cell proliferation and OB differentiation and increases adipocyte formation, resulting in a trabecular bone loss. Mechanistically, YAP interacts with β-catenin and is necessary for maintenance of nuclear β-catenin level and Wnt/β-catenin signaling. Expression of β-catenin in YAP-deficient BMSCs（bone marrow stromal cells） diminishes the osteogenesis deficit. These results thus identify YAP-β-catenin as an important pathway for osteogenesis during adult bone remodeling and uncover a mechanism underlying YAP regulation of bone homeostasis.
基金Supported by Grants from the National Natural Science Foundation of China(Key program 30930027)Natural Science Foundation of Guangdong Province(No.8151503102000032)
文摘AIM: To study the metabolic profile of human umbilical mesenchymal stem cells (HUMSC) and adipogenic differentiation by nuclear magnetic resonance (NMR) spectroscopy.
文摘Obesity is a major human health problem associated with various diseases, including cardiac injury and type 2 diabetes. Trapa japonica Flerov (TJF) has been used in traditional oriental medicine to treat diabetes. In this study, we evaluated the inhibitory effect of and the mechanism underlying the effect of TJF extract on adipogenesis in 3T3-L1 cells. The effects of TJF extract on cell viability were analyzed using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, and the anti-adipogenic effect was measured by oil red O staining. The expression of peroxisomal proliferator activated receptor (PPAR)γ, CCAAT/enhancer-binding protein-α (C/EBP)α, adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), adiponectin, and fatty acid binding protein (FABP)4 involved in adipogenesis was determined by western blot analysis. TJF extract effectively inhibited lipid accumulation and the expression of PPARγ and C/EBPα in 3T3-L1 cells. TJF also increased the phosphorylation of AMPK and ACC, and decreased the expression of adiponectin and FABP4. These results indicate that TJF extract exerts its anti-obesity effect through the downregulation of adipogenic transcription factors and adipogenic marker genes.
基金This study is supported by grants from the National Natural Science Foundation of China(81274041 and 81503540)the International Cooperation Projects of MOE(2011DFA30920)+1 种基金a Co-construction Project of Beijing Board of Education(0101216-14)a Research Project of the Beijing University of Chinese Medicine(2014-X-003).
文摘Objective:To determine the effect of Salvianolic acid B (Sal B) on glucose and lipid metabolism in mice with high-fat diet (HFD)-induced obesity,and to investigate the underlying mechanisms by measuring the expression levels of key adipogenic transcription factors.Methods:Six-week-old C57BL/6J male mice were fed for 12 weeks with a HFD to induce obesity or a standard diet to serve as normal controls.A mean body weight increase of more than 20% after these 12 weeks was used as the criteria for obesity.HFD-fed obese mice then received a supplement of Sal B (100 mg/kg body weight/day),metformin (75 mg/kg body weight/day) or water (an equivalent volume;served as model controls) by oral gavage for an additional 8 weeks,and the normal controls received water (an equivalent volume) by oral gavage for the same period.Results:Sal B significantly reduced body weight gain (P <.05) without influencing food intake in HFD-fed obese mice relative to model controls.Sal B also reduced the body fat mass of the obese mice relative to model controls in a time-dependent manner (P <.05).Sal B significantly decreased the serum concentrations of low-density lipoprotein cholesterol,total cholesterol,triglyceride and free fatty acids by 25.5%,20.2%,20.6% and 13.4%,respectively,and increased the concentration of high-density lipoprotein cholesterol by 50.1% relative to model controls.In addition,Sal B significantly lowered fasting glucose concentrations and improved insulin sensitivity relative to model controls (P <.05).Sal B acted by ameliorating the histopathological changes in both brown and white adipose tissues of obese mice.Moreover,in brown adipose tissue,Sal B up-regulated the mRNA and protein expression of PPARγ and c/EBPα,and the protein expression of PPARα and SREBP-1 (P <.05).In white adipose tissue,Sal B down-regulated the mRNA expression of PPARγ and c/EBPα,and decreased the protein expression of PPARγ and SREBP-1(P <.05).Conclusjons:The results suggest that Sal B can reduce body weight gain and regulate glucose and lipid metabolism in mice with diet-induced obesity by regulating adipogenic transcription factors in their adipose tissues.
基金Supported by Basic and Applied Basic Research Foundation of Guangdong Province,No.2020A1515010123 and No.2021A1515010695Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province,No.2019A030317011.
文摘BACKGROUND Osteoporosis(OP)has become a major public health problem worldwide.Most OP treatments are based on the inhibition of bone resorption,and it is necessary to identify additional treatments aimed at enhancing osteogenesis.In the bone marrow(BM)niche,bone mesenchymal stem cells(BMSCs)are exposed to a hypoxic environment.Recently,a few studies have demonstrated that hypoxiainducible factor 2alpha(HIF-2α)is involved in BMSC osteogenic differentiation,but the molecular mechanism involved has not been determined.AIM To investigate the effect of HIF-2αon the osteogenic and adipogenic differentiation of BMSCs and the hematopoietic function of hematopoietic stem cells(HSCs)in the BM niche on the progression of OP.METHODS Mice with BMSC-specific HIF-2αknockout(Prx1-Cre;Hif-2αfl/fl mice)were used for in vivo experiments.Bone quantification was performed on mice of two genotypes with three interventions:Bilateral ovariectomy,semilethal irradiation,and dexamethasone treatment.Moreover,the hematopoietic function of HSCs in the BM niche was compared between the two mouse genotypes.In vitro,the HIF-2αagonist roxadustat and the HIF-2αinhibitor PT2399 were used to investigate the function of HIF-2αin BMSC osteogenic and adipogenic differentiation.Finally,we investigated the effect of HIF-2αon BMSCs via treatment with the mechanistic target of rapamycin(mTOR)agonist MHY1485 and the mTOR inhibitor rapamycin.RESULTS The quantitative index determined by microcomputed tomography indicated that the femoral bone density of Prx1-Cre;Hif-2αfl/fl mice was lower than that of Hif-2αfl/fl mice under the three intervention conditions.In vitro,Hif-2αfl/fl mouse BMSCs were cultured and treated with the HIF-2αagonist roxadustat,and after 7 d of BMSC adipogenic differentiation,the oil red O staining intensity and mRNA expression levels of adipogenesis-related genes in BMSCs treated with roxadustat were decreased;in addition,after 14 d of osteogenic differentiation,BMSCs treated with roxadustat exhibited increased expression of osteogenesis-related genes.The opposite effects were shown for mouse BMSCs treated with the HIF-2αinhibitor PT2399.The mTOR inhibitor rapamycin was used to confirm that HIF-2αregulated BMSC osteogenic and adipogenic differentiation by inhibiting the mTOR pathway.Consequently,there was no significant difference in the hematopoietic function of HSCs between Prx1-Cre;Hif-2αfl/fl and Hif-2αfl/fl mice.CONCLUSION Our study showed that inhibition of HIF-2αdecreases bone mass by inhibiting the osteogenic differentiation and increasing the adipogenic differentiation of BMSCs through inhibition of mTOR signaling in the BM niche.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 81071520）.
文摘Background Steroids inhibit osteogenic differentiation and decrease bone formation while concomitantly inducing adipose deposition in osteocytes.This leads to the fatty degeneration and necrosis of bone cells commonly seen in osteonecrosis of the femoral head.The peroxisome proliferator-activated receptor-γ （PPARγ） is an adipogenic transcription factor linked to the development of this disease and responsible for inducing adipogenesis over osteogenesis in bone marrow mesenchymal stem cells （BMSCs）.The aim of this study was to assess whether adipogenic differentiation could be suppressed,and thus osteogenic potential retained,by inhibiting PPARy expression in BMSCs.Methods Cells from the bone marrow of New Zealand rabbits were treated with 10-7 mol/L dexamethasone and infected with one of three small interference RNA （siRNA） adenovirus vectors （S1,S2,and S3） or non-targeting control siRNA （Con） and compared with dexamethasone-treated （model） and untreated （normal） cells.Cells were grown for 21 days and stained with Sudan Ⅲ for adipocyte formation.At various time points,cells were also assessed for changes in PPARγ,osteocalcin （OC）,Runx2,alkaline phosphatase （ALP） activity,and triglyceride （TG） content.Results Dexamethasone-treated model and control groups showed a significant increase in fatty acid-positive staining,which was inhibited in cells treated with PPARγ siRNA-treated,similar to normal untreated cells.All three siRNA groups significantly inhibited PPARγ mRNA and protein,adipocyte number,and TG content compared with the dexamethasonetreated model and control groups,matching that seen in normal cells.OC and Runx2 mRNA and protein,as well as ALP activity,were significantly higher in cells treated with siRNA against PPARγ,similar to that seen in the normal cells.These osteogenic markers were significantly lower in the dexamethasone-treated cell cultures.Conclusions The siRNA adenovirus vector targeting PPARγ can efficiently inhibit steroid-induced adipogenic differentiation in rabbit BMSCs and retain their osteogenic differentiation potential.
基金supported by the National Natural Science Foundation of China (Grant No.30972119)
文摘Porcine mesenchymal stem cells in postnatal muscle have been demonstrated to differentiate into adipocytes. This increases adipocyte number and lipid accumulation, and is thought to be the origin of intramuscular fat. In this study, the effects of myostatin and arginine on adipogenic differentiation in mesenchymal stem cells derived from porcine muscle （pMDSCs） were investigated in vitro. Intracellular triglyceride levels were reduced by exogenous myostatin and increased by arginine supplementation or myostatin antibody （P〈0.01）. The inhibition of lipid accumulation by rnyostatin in pMDSCs was alleviated by arginine supplementation （P〈0.01）. Expression patterns of adipogenic transcription factors showed that exogenous myostatin suppressed PPAR72 and aP2 expression （P〈0.01）, while supplemental arginine or myostatin antibody promoted ADD1 expression （P〈0.01）. Furthermore, compared with the addition of either myostatin protein or antibody alone, ADD1 and PPARδ expression were promoted by the combination of arginine and myostatin （P〈0.01）, and arginine combined with myostatin antibody promoted the expression of ADD1, PPARδ, C/EBPα, PPARγ2 and LPL in pMDSCs （P〈0.05）. These results suggest that myostatin inhibits adipogenesis in pMDSCs, and that this can be alleviated by arginine supplementation, at least in part, through promoting ADD1 and PPARδ expression.
文摘Extracellular matrix （ECM） plays a very important role in regulating cell function and fate. It is highly desirable to fabricate biomimetic models to investigate the role of ECM in stem cell differentiation. In this study, arginine- glycine--aspartate （RGD）-modified gold nanoparticles （Au NPs） with tunable surface ligand density were prepared to mimic the ECM microenvironment. Their effect on osteogenic and adipogenic differentiation of human mesenchymal stem cells （MSCs） was investigated. The biomimetic Au NPs were taken up by MSCs in a ligand density-dependent manner. The biomimetic NPs with a high RGD density had an inhibitive effect on the alkaline phosphatase （ALP） activity, calcium deposition, and osteogenic marker gene expression of MSCs. Their effect on oil droplet formation and adipogenic marker gene expression was negative when RGD density was low, while their effect was promotive when RGD density was high. The biomimetic Au NPs regulated the osteogenic and adipogenic differentiation of MSCs mainly through affecting the focal adhesion and cytoskeleton. This study highlights the roles of biomimetic NPs on stem cell differentiation that could provide a meaningful strategy in fabricating functional biomaterials for tissue engineering and biomedical applications.
基金Project supported by the National Natural Science Foundation of China (20971034)Foundation for Key Program of Ministry of Education of China (208018)+2 种基金Returned Scholars of Hebei Province (207041)Natural Science Key Foundation of Hebei Province (B2009000161)Natural Science Foundation of Hebei University
文摘In order to elucidate the action of La3＋ on bone metabolism,effects of La3＋ on the osteogenic and adipogenic differentiation of pri-mary mouse bone marrow stromal cells（BMSCs） were studied by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide（MTT） test,alkaline phosphatase（ALP） activity measurement,mineralized function,oil red O stain and measurement.The results showed that La3＋ pro-moted the proliferation of BMSCs except at 1×10-10 and 1×10-6 mol/L.The effect of La3＋ on the osteogenic differentiation depended on con-centrations at the 7th day,but the osteogenic differentiation was inhibited at any concentration at the 14th day.La3＋ promoted the formation of mineralized matrix nodules except at 1×10-8 and 1×10-5 mol/L.La3＋ inhibited adipogenic differentiation except at 1×10-10 and 1×10-7 mol/L at the 10th day,and inhibited adipogenic differentiation except at 1×10-9 mol/L at the 16th day.These findings suggested that La3＋ might have protective effect on bone at appropriate dose and time.This would be valuable for better understanding the mechanism of the effect of La3＋ on bone metabolism.
基金Project supported by the National Natural Science Foundation of China(51972148,51802115,11904131,21501090)the Project of"20 items of University"of Jinan(2018GXRC031)the Doctoral Fund of University of Jinan(XBS1609)。
文摘Mesenchymal stem cells(MSCs)are multi-potent cells that are able to differentiate and mature into various types of cells under a certain microenvironment for cell therapy and tissue regeneration.Scandium(Sc),an important rare earth element,recently has been intensively investigated in biomedical fields as well as industrial engineering,and chloride channels have been proven to be able to affect osteogenic differentiation.Thus,it is significant to investigate effects of ScCl_(3)on cell activities of MSCs.In this paper,rat bone MSCs(rBMSCs)were co-cultured with various concentrations of ScCl_(3)(1×10^(-8),1×10^(-6),and 1×10^(-4)mol/L)to evaluate their influence on cell proliferation as well as osteogenic and adipogenic differentiation in vitro.The results indicate that ScCl_(3)promotes the proliferation of rBMSCs initially,which is yet reduced upon ion accumulation.We used immunofluorescence staining,quantitative real time polymerase chain reactions,and assays measuring alkaline phosphatase activity,mineralized deposits,and intracytoplasmic lipids to reveal that rBMSCs treated with ScCl_(3)at concentrations of 1×10^(-8)-1×10^(-6)mol/L can enhance levels of osteogenic differentiation in a dosedependent manner and reduce adipogenic differentiation to a certain degree through Wnt/β-catenin signaling pathway.These results indicate that appropriate concentrations of ScCl_(3)can improve osteogenic differentiation in the lineage commitment of rBMSCs,and thus,promote bone remodeling.This study implies that ScCl_(3) possesses great potentials in the treatment of bone diseases and would provide new strategy of designing composites by SiCl3 doping for biomedical applications in the future.
文摘The retinoblastoma gene product(pRb)is a chromatin-associated protein that can either suppress or promote activity of key regulators of tissue-specific differentiation.We found that twelve weeks after transfection of the exogenous active(ΔB/X andΔр34)or inactive(ΔS/N)forms of RB into the 10T1/2 mesenchymal stem cells and clonal selection not a single cell line did contain exogenous RB,despite being G-418 resistant.However,the consequences of the transient production of exogenous RB had different effects on the cell fate.TheΔB/X andΔр34 cells transfected with active form of RB showed elevated levels of inducible adipocyte differentiation(AD).On the contrary,theΔS/N cells transfected with inactive RB mutant were insensitive to induction of AD associated with abolishing of expression of the PPARγ2.Additionally,the PPARγ2 promoter in undifferentiatedΔS/N cells was hypermethylated,but all except−60 position CpG became mostly demethylated after cells exposure to AD.We conclude that while transient expression of inactive exogenous RB induces long term epigenetic alterations that prevent adipogenesis,production of active exogenous RBs results in an AD-promoting epigenetic state.These results indicate that pRb is involved in the establishment of hereditary epigenetic memory at least by creating a methylation pattern of PPARγ2.
基金supported by a grant from UGC Area of Excellence project "Chinese Medicine Research and Further Development"(No.AoE/B-10/01)the Shenzhen Key Laboratory Funding Scheme of Shenzhen Municipal Government, Shenzhen Double Hundred Project
文摘Imipramine （IM） has been widely used clinically for the treatment of mental disorders. Its actions on tissues or organs other than the nervous system also need to be understood for its proper clinical use. In this study, the effects of IM on adipogenic differentiation in both 3T3-L1 preadipocytes and mouse marrow stromal cells （MSCs） were investigated. The results showed that fewer adipocytic cells were developed from 3T3-L1 preadipocytes in the presence of 0.001 to 1 μmol/L of IM as compared to control. Similar inhibitory effect was also observed in mouse MSCs. The decrease in the formation of adipocytes was accompanied with significant down-regulation at mRNA expression of the early adipogenic transcription factor, peroxisome proliferator-activated receptor γ2 （PPARγ2）. Western blot analysis further revealed that the protein expression of PPARγ2 was reduced markedly in ceils treated with IM at concentrations of 0.01, 0.1 and 1 μmol/L, suggesting that the suppression on PPAR72 was involved in IM＇s inhibition on MSCs adipogenesis. Moreover, IM at the above concentrations could stimulate the mRNA expression of β2-adrenergic receptor （AR） and β3-AR, which implicated that the effect of IM on adipogenic differentiation was partially mediated by β-ARs. Our results demonstrated for the first time that the conventional antidepressive imipramine exerts accompanied inhibitory effect on adipocyte formation, which may have possible clinical implications.
基金supported by National Natural Science Foundation of China(No.81160508)The Science and Technology Landing Program Project of Colleges and University in Jiangxi Province(KJLD14058)
文摘Objective：The study was designed to investigate the molecular mechanism of quercitrin on osteogenic differentiation and adipogenic differentiation of r BMSCs.Methods：r BMSCs were harvested from SD rats,and determination of alkaline phosphatase（ALP）activity,quantification of mineralization by Alizarin Red S staining,and the m RNA expression of osteogenic differentiation markers（Runx2,BMP-2,and OSX）by RT-PCR after r BMSCs stimulated by osteogenic induction with（0.1–10）μg/m L of quercitrin,quantification of Lipid droplet by Oil Red O staining and the m RNA expression of adipogenic differentiation marker（,and a P2）by RT-PCR after r BMSCs stimulated by adipogenic induction with（0.1-10）μg/m L of quercitrin.Results：Quercitrin can up-regulate the m RNA expression of osteogenic differentiation markers（Runx2,BMP-2,and OSX）and increase ALP activity and mineralization after osteogenic induction,on the other hand quercitrin can suppress the m RNA expression of adipogenic differentiation markers（,and a P2）and decrease lipid droplet after adipogenic induction.Conclusion：This study suggested that quercitrin not only stimulated osteogenic differentiation but also inhibited adipogenic differentiation of r BMSCs,which was associated with the up-regulation of Runx2,BMP-2,and OSX m RNA expression and the down-regulation of,and a P2 m RNA expression.
基金supported by the grants of National Natural Science Foundation of China(No.31271027 and No.81171475).
文摘Aim:To evaluate the age-related effects on the adipogenic differentiation and proliferation potentials of human orbital adipose-derived stem cells(OASCs).Methods:Orbital adipose samples were harvested from the central fat compartment in the lower eyelids of 10 young and middle-aged patients during routine blepharoplasty surgery.After assessment of the morphological changes of adipocytes with aging,OASCs were isolated from the fat samples and expanded in vitro.Differences in the stem cell colony number(fibroblast colony-forming unit),growth rate and phenotype characterization(flow cytometry analysis)were evaluated.The ability of OASCs to differentiate into adipocytes was determined by oil red O staining and the mRNA expression level of peroxisome proliferator-activated receptorγ.Results:Fat cell size showed a decreasing trend with advancing age.Although no difference was found in the expression of cell surface markers,the colony number and proliferative rate of OASCs from middle-aged donors were significantly lower than those from the young donors.The adipogenic differentiation capacity of middle-aged OASCs was also reduced.These differences were statistically significant(P<0.001).Conclusion:The data showed that the progenitor cell number,proliferation capacity and adipogenic potential of OASCs decreased with aging,suggesting that using OASCs from elderly patients for therapeutic purposes might be restricted.
基金supported by the Agriculture and Food Research Initiative Competitive Grants(No.2015-67015-23219 and 2016-68006-24634)from the USDA National Institute of Food and Agriculture.
文摘Over the past few decades,genetic selection and refined nutritional management have extensively been used to increase the growth rate and lean meat production of livestock.However,the rapid growth rates of modern breeds are often accompanied by a reduction in intramuscular fat deposition and increased occurrences of muscle abnor‑malities,impairing meat quality and processing functionality.Early stages of animal development set the long‑term growth trajectory of offspring.However,due to the seasonal reproductive cycles of ruminant livestock,gestational nutrient deficiencies caused by seasonal variations,frequent droughts,and unfavorable geological locations nega‑tively affect fetal development and their subsequent production efficiency and meat quality.Therefore,enrolling live‑stock in nutritional intervention strategies during gestation is effective for improving the body composition and meat quality of the offspring at harvest.These crucial early developmental stages include embryonic,fetal,and postnatal stages,which have stage‑specific effects on subsequent offspring development,body composition,and meat quality.This review summarizes contemporary research in the embryonic,fetal,and neonatal development,and the impacts of maternal nutrition on the early development and programming effects on the long‑term growth performance of livestock.Understanding the developmental and metabolic characteristics of skeletal muscle,adipose,and fibrotic tissues will facilitate the development of stage‑specific nutritional management strategies to optimize production efficiency and meat quality.
基金the National Natural Science Foundation of China(Grant Nos.22276221,21675176)the Fundamental Research Funds for the Central Universities,and South-Central Minzu University(Grant No.CZP21002)for financial support.
文摘Bone marrow mesenchymal stem cells(BMSCs)are non-hematopoietic multipotent stem cells capable of differentiating into mature cells.Isoquercetin,an extract from natural sources,has shown promise as a potential treatment for osteoporosis.To investigate the therapeutic effects of isoquercetin on osteoporosis,bone marrow mesenchymal stem cells(BMSCs)were cultured in vitro,and osteogenesis or adipogenesis was induced in the presence of isoquercetin for 14 days.We evaluated cell viability,osteogenic and adipogenic differentiation,as well as mRNA expression levels of Runx2,Alpl,and OCN in osteoblasts,and mRNA expression levels of Pparγ,Fabp4,and Cebpαin adipocytes.The results showed that isoquercetin dose-dependently increased cell viability and promoted osteogenic differentiation,as evidenced by Alizarin Red and alkaline phosphatase staining and mRNA expression levels of Runx2,Alpl,and OCN in osteoblasts(P<0.05).In contrast,isoquercetin inhibited adipogenic differentiation and decreased the mRNA expres-sion levels of Pparγ,Fabp4,and Cebpαin adipocytes(P<0.05).In vivo,isoquercetin treatment increased bone quan-tity and density in an osteoporosis model mice group,as determined byμCT scanning and immunohistochemistry(P<0.05).These findings suggest that isoquercetin may have therapeutic potential for osteoporosis by promoting the proliferation and differentiation of BMSCs towards osteoblasts while inhibiting adipogenic differentiation.
基金This work was supported by The Nature Science Foundation of China(Nos.82070176,82070128,81900132)the Medical Science and Technology Research Fund of Guangdong Province(No.A2020585).
文摘The pathogenesis of myelodysplastic syndrome(MDS)may be related to the abnormal expression of microRNAs(miRNAs),which could influence the differentiation capacity of mesenchymal stem cells(MSCs)towards adipogenic and osteogenic lineages.In this study,exosomes from bone marrow plasma were successfully extracted and identified.Assessment of miR-103-3p expression in exosomes isolated from BM in 34 MDS patients and 10 controls revealed its 0.52-fold downregulation in patients with MDS compared with controls(NOR)and was downregulated 0.55-fold in MDS-MSCs compared with NOR-MSCs.Transfection of MDS-MSCs with the miR-103-3p mimic improved osteogenic differentiation and decreased adipogenic differentiation in vitro,while inhibition of miR-103-3p showed the opposite results in NOR-MSCs.Thus,the expression of miR-103-3p decreases in MDS BM plasma and MDS-MSCs,significantly impacting MDS-MSCs differentiation.The miR-103-3p mimics may boost MDS-MSCs osteogenic differentiation while weakening lipid differentiation,thereby providing possible target for the treatment of MDS pathogenesis.
基金supported by the National key research and development program of China(Grant No.2018YFD0500402)the National Natural Science Foundation of China(Grant No.31790412,Grant No.31672431)the National Key Basic Research Program of China(2013CB127302。
文摘Background:Long non-coding RNAs(lncRNAs)are emerging key regulators involved in a variety of biological processes such as cell differentiation and development.The balance between myogenesis and adipogenesis is crucial for skeletal muscle homeostasis in humans and meat quality in farm animals.The present study aimed to reveal the global transcriptomic profiles of adipogenic(Adi-)and myogenic(Myo-)precursors derived from porcine skeletal muscle and identify lncRNAs involved in the modulation of myogenesis homeostasis in porcine skeletal muscle.Results:In this study,a total of 655 novel individual lncRNAs including differentially expressed 24 lncRNAs,and 755 differentially expressed mRNAs were identified(fold change≥2 or≤0.5 and adjusted P<0.05).Integrated results of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis accompanied by the variation of intracellular Ca2+concentration highlighted Lnc-ADAMTS9 involved in the modulation of myogenesis homeostasis in porcine skeletal muscle.Although Lnc-ADAMTS9 knock-down did not alter the mRNA expression of ADAMTS9,we demonstrated that Lnc-ADAMTS9 can promote myogenic proliferation and myogenic differentiation of myogenic precursors through inhibiting the ERK/MAPK signaling pathway.Conclusion:We deciphered a comprehensive catalog of mRNAs and lncRNAs that might be involved in the regulation of myogenesis and adipogenesis homeostasis in the skeletal muscle of pigs.The Lnc-ADAMTS9 exerts an essential role in myogenesis through the ERK signaling pathway.
