BACKGROUND Bone disease is an under-recognized cause of morbidity in chronic pancreatitis(CP).Over the past decade,publications of original studies on bone disease in CP has warranted synthesis of the evidence to asce...BACKGROUND Bone disease is an under-recognized cause of morbidity in chronic pancreatitis(CP).Over the past decade,publications of original studies on bone disease in CP has warranted synthesis of the evidence to ascertain the true burden of the problem.AIM To quantify the prevalence of osteopenia,osteoporosis,and fragility fractures in CP patients and investigate the associated clinical features and outcomes.METHODS A systematic search identified studies investigating bone disease in CP patients from Cochrane Library,Embase,Google Scholar,Ovid Medline,PubMed,Scopus,and Web of Science,from inception until October 2022.The outcomes included prevalence of osteopenia,osteoporosis,and fragility fractures,which were metaanalyzed using a random-effects model and underwent metaregression to delineate association with baseline clinical features.RESULTS Twenty-one studies were included for systematic review and 18 studies were included for meta-analysis.The pooled prevalence of osteopenia and osteoporosis in CP patients was 41.2%(95%CI:35.2%-47.3%)and 20.9%(95%CI:14.9%-27.6%),respectively.The pooled prevalence of fragility fractures described among CP was 5.9%(95%CI:3.9%-8.4%).Metaregression revealed significant association of pancreatic enzyme replacement therapy(PERT)use with prevalence of osteoporosis[coefficient:1.7(95%CI:0.6-2.8);P<0.0001].We observed no associations with mean age,sex distribution,body mass index,alcohol or smoking exposure,diabetes with prevalence of osteopenia,osteoporosis or fragility fractures.Paucity of data on systemic inflammation,CP severity,and bone mineralization parameters precluded a formal metaanalysis.CONCLUSION This meta-analysis confirms significant bone disease in patients with CP.Other than PERT use,we observed no patient or study-specific factor to be significantly associated with CP-related bone disease.Further studies are needed to identify confounders,at-risk population,and to understand the mechanisms of CP-related bone disease and the implications of treatment response.展开更多
Substantial evidence exists that in addition to the well-known complications of diabetes, increased fracture risk is an important morbidity. This risk is probably due to altered bone properties in diabetes. Circulatin...Substantial evidence exists that in addition to the well-known complications of diabetes, increased fracture risk is an important morbidity. This risk is probably due to altered bone properties in diabetes. Circulating biochemical markers of bone turnover have been found to be decreased in type 2 diabetes （T2D） and may be predictive of fractures independently of bone mineral density （BMD）. Serum sclerostin levels have been found to be increased in T2D and appear to be predictive of fracture risk independent of BMD. Bone imaging technologies, including trabecular bone score （TBS） and quantitative CT testing have revealed differences in diabetic bone as compared to non-diabetic individuals. Specifically, high resolution peripheral quantitative CT （HRpQCT） imaging has demonstrated increased cortical porosity in diabetic postmenopausal women. Other factors such as bone marrow fat saturation and advanced glycation endproduct （AGE） accumulation might also relate to bone cell function and fracture risk in diabetes. These data have increased our understanding of how T2D adversely impacts both bone metabolism and fracture risk.展开更多
Bone is a complex tissue that undergoes constant remodeling to maintain homeostasis,which requires coordinated multilineage differentiation and proper proliferation of mesenchymal stromal cells(MSCs).Mounting evidence...Bone is a complex tissue that undergoes constant remodeling to maintain homeostasis,which requires coordinated multilineage differentiation and proper proliferation of mesenchymal stromal cells(MSCs).Mounting evidence indicates that a disturbance of bone homeostasis can trigger degenerative bone diseases,including osteoporosis and osteoarthritis.In addition to conventional genetic modifications,epigenetic modifications(i.e.,DNA methylation,histone modifications,and the expression of noncoding RNAs)are considered to be contributing factors that affect bone homeostasis.Long noncoding RNAs(lncRNAs)were previously regarded as‘transcriptional noise’with no biological functions.However,substantial evidence suggests that lncRNAs have roles in the epigenetic regulation of biological processes in MSCs and related diseases.In this review,we summarized the interactions between lncRNAs and epigenetic modifiers associated with osteo-/adipogenic differentiation of MSCs and the pathogenesis of degenerative bone diseases and highlighted promising lncRNA-based diagnostic and therapeutic targets for bone diseases.展开更多
Metastatic bone disease of the distal extremities,also known as acrometastasis,is very rare.Thus,there is very limited information regarding the clinical manifestations and methods of surgical treatment.The current av...Metastatic bone disease of the distal extremities,also known as acrometastasis,is very rare.Thus,there is very limited information regarding the clinical manifestations and methods of surgical treatment.The current available literature shows that acrometastases are often encountered in the context of advanced disease and are thus associated with poor patient survival.As metastatic bone disease is generally uncurable,the goal of surgical treatment is to provide the patient with good function with as few complications as possible.In this article,we discuss the clinical manifestation of acrometastases,the methods of surgical intervention,and the expected clinical outcome.Non-surgically managed pathological fractures generally remain ununited;therefore,conservative treatment is reserved for patients with poor general condition or dismal prognosis.The current evidence suggests that in lesions of the lower arm and leg,osteosynthesis(plate and screw fixation or intramedullary nail)is the most common method of reconstruction,whereas local excision or amputation are more commonly used in cases of more distal lesions(such as ankle,foot and hand).Following surgery most patients receive adjuvant radiotherapy,even though its role is poorly documented.Close collaboration between orthopedic surgeons and medical oncologists is necessary to improve patient care and treatment outcome.Further studies are needed in order to provide stronger clinical evidence and improve decision-making,in an effort to optimize the patients’quality of life and avoid the need for revision surgery.展开更多
BACKGROUND The neutrophil-lymphocyte ratio(NLR)is often used to predict a poor prognosis in patients with tumors.This study investigated the preoperative peripheral blood NLR in predicting postoperative survival(POS)i...BACKGROUND The neutrophil-lymphocyte ratio(NLR)is often used to predict a poor prognosis in patients with tumors.This study investigated the preoperative peripheral blood NLR in predicting postoperative survival(POS)in patients with multiple myeloma bone disease(MMBD).AIM To evaluate whether NLR can be used to predict the prognosis of MMBD patients after surgery.METHODS The clinical data of 82 MMBD patients who underwent surgical treatments in Beijing Chao-yang Hospital were collected.The NLR was obtained from the absolute number of neutrophils and lymphocytes,calculated by the number of neutrophils and divided by the number of lymphocytes.The peripheral blood lymphocyte percentage was used as the major marker to analyze the change in characteristics of the immune statuses of multiple myeloma patients.RESULTS The NLR cut-off values of NLR≥3 patients and NLR≥4 patients were significantly correlated with POS.The 3-and 5-year cumulative survival rates of the high NLR group(NLR≥3 patients)were 19.1%and 0.0%,respectively,which were lower than those of the low NLR group(NLR<3 patients)(67.2%and 48.3%)(P=0.000).In the high NLR group,POS(14.86±14.28)was significantly shorter than that in the low NLR group(32.68±21.76).Univariate analysis showed that the lymphocyte percentage 1 wk after the operation(19.33±9.08)was significantly lower than that before the operation(25.72±11.02).Survival analysis showed that postoperative chemotherapy,preoperative performance status and preoperative peripheral blood NLR≥3 were independent risk factors for POS.CONCLUSION The preoperative peripheral blood NLR can predict POS in MMBD patients.MMBD patients with a high preoperative NLR(NLR≥3)showed poor prognosis.展开更多
This is a retrospective analysis of long-term efficacy of parathyroidectomy on hyperparathyroid bone disease. The clinical manifestations, bone structure, and bone mineral density in 16 patients averaged 5.1 (1. 0-10....This is a retrospective analysis of long-term efficacy of parathyroidectomy on hyperparathyroid bone disease. The clinical manifestations, bone structure, and bone mineral density in 16 patients averaged 5.1 (1. 0-10. 5) years after parathyroidectomy were assessed. The results showed that although the bone disease could be markedly relieved after surgery, yet at terminal point of follow-up, 10/16 cases (62. 5% ) got incomplete recovery of bone disease, the ratio of incomplete recovery in Y1 group with severe bone disease was higher than that of Y2 group with mild bone disease (P <0. 05). The concentrations of serum BGP and morning void urine pyridinoline were within the refer ence ranges of young and middle aged controls. These imply that the osteoblastic and osteoclastic activities had reached a balancing state. The results suggested that hyperparathyroid patients should be operated on as early as possible, and intensively followed up after operation. subsequent therapy should be given to patients with incomplete recovery of bone disease.展开更多
Vanishing bone disease(Gorham-Stout syndrome) is a rare entity of unknown etiology, characterized by de struction of osseous matrix and proliferation of vascula structures, resulting in destruction and absorption o bo...Vanishing bone disease(Gorham-Stout syndrome) is a rare entity of unknown etiology, characterized by de struction of osseous matrix and proliferation of vascula structures, resulting in destruction and absorption o bone. Despite the extensive investigation of the patho genetic mechanisms of the disease, its etiology hasn'been clarified and several theories exist. The syndrome can affect one or multiple bones of the patient, includ ing the skull, the upper and lower extremities, the spine and pelvis. The clinical presentation of a patient suffer ing from vanishing bone disease includes, pain, func tional impairment and swelling of the affected region although asymptomatic cases have been reported, as well as cases in which the diagnosis was made after a pathologic fracture. In this short review we summarize the theories regarding the etiology as well as the clini cal presentation, the diagnostic approach and treat ment options of this rare disease.展开更多
Multiple myeloma is a hematological malignancy inwhich clonal plasma cells proliferate and accumulate within the bone marrow. The presence of osteolytic le-sions due to increased osteoclast(OC) activity and sup-presse...Multiple myeloma is a hematological malignancy inwhich clonal plasma cells proliferate and accumulate within the bone marrow. The presence of osteolytic le-sions due to increased osteoclast(OC) activity and sup-pressed osteoblast(OB) function is characteristic of the disease. The bone marrow mesenchymal stromal cells(MSCs) play a critical role in multiple myeloma patho-physiology, greatly promoting the growth, survival, drug resistance and migration of myeloma cells. Here, we specifically discuss on the relative contribution of MSCs to the pathophysiology of osteolytic lesions in light of the current knowledge of the biology of my-eloma bone disease(MBD), together with the reported genomic, functional and gene expression differences between MSCs derived from myeloma patients(pMSCs) and their healthy counterparts(dMSCs). Being MSCs the progenitors of OBs, pMSCs primarily contribute to the pathogenesis of MBD because of their reduced osteogenic potential consequence of multiple OB inhibi-tory factors and direct interactions with myeloma cells in the bone marrow. Importantly, pMSCs also readily contribute to MBD by promoting OC formation and ac-tivity at various levels(i.e., increasing RANKL to OPG expression, augmenting secretion of activin A, uncou-pling ephrinB2-EphB4 signaling, and through augment-ed production of Wnt5a), thus further contributing to OB/OC uncoupling in osteolytic lesions. In this review, we also look over main signaling pathways involved in the osteogenic differentiation of MSCs and/or OB activity, highlighting amenable therapeutic targets; in parallel, the reported activity of bone-anabolic agents(at preclinical or clinical stage) targeting those signaling pathways is commented.展开更多
Bone disease(osteopenia or osteoporosis)is a highly prevalent condition in society and presents a tremendous,preventable public health burden.Screening procedures,such as,dual-energy X-ray absorptiometry scans,have al...Bone disease(osteopenia or osteoporosis)is a highly prevalent condition in society and presents a tremendous,preventable public health burden.Screening procedures,such as,dual-energy X-ray absorptiometry scans,have allowed early identification and intervention to improve bone health,and reduce the risk of osteoporotic fractures,which carry significant morbidity and mortality.The association of bone disease has been recognized in several diseases of the gastrointestinal tract,resulting in established guidelines for screening in patients with malabsorptive disorders such as inflammatory bowel disease and celiac disease.Increasingly,the risk of bone disease has been recognized in patients with chronic pancreatitis(CP),who share similar risk factors as patients with other high gastrointestinal disorders.As a result,there have been a number of studies examining the prevalence and risks of bone disease and fractures in patients with CP.This review aims to summarize the recent literature and current recommendations related to bone disease in CP.展开更多
Neuroprotection and neuroregeneration are two of the most promising disease-modifying ther- apies for the incurable and widespread Parkinson＇s disease. In Parkinson＇s disease, progressive degeneration of nigrostriat...Neuroprotection and neuroregeneration are two of the most promising disease-modifying ther- apies for the incurable and widespread Parkinson＇s disease. In Parkinson＇s disease, progressive degeneration of nigrostriatal dopaminergic neurons causes debilitating motor symptoms. Neurotrophic factors play important regulatory roles in the development, survival and maintenance of specific neuronal populations. These factors have the potential to slow down, halt or reverse the loss of nigrostriatal dopaminergic neurons in Parkinsoffs disease. Several neurotrophic fac- tors have been investigated in this regard. This review article discusses the neurodevelopmental roles and therapeutic potential of three dopaminergic neurotrophic factors： glial cell line-derived neurotrophic factor, neurturin and growth/differentiation factor 5.展开更多
Idiopathic hypercalciuria （IH） is the leading metabolic risk factor for urolithiasis and affects all age groups without gender or race predominance. IH has a high morbidity with or without lithiasis and reduced bone...Idiopathic hypercalciuria （IH） is the leading metabolic risk factor for urolithiasis and affects all age groups without gender or race predominance. IH has a high morbidity with or without lithiasis and reduced bone mineral density （BMD）, as described previously in pe-diatric patients as well as in adults. The pathogenesis of IH is complex and not completely understood, given that urinary excretion of calcium is the end result of an interplay between three organs （gut, bone and kidney）, which is further orchestrated by hormones, such as 1,25 dihydroxyvitamin D, parathyroid hormone, calcitonin and fosfatonins （i.e., fbroblast growth-factor-23）. Usu-ally, a primary defect in one organ induces compensa-tory mechanisms in the remaining two organs, such as increased absorption of calcium in the gut secondary toa primary renal loss. Thus, IH is a systemic abnormality of calcium homeostasis with changes in cellular trans-port of this ion in intestines, kidneys and bones. Re-duced BMD has been demonstrated in pediatric patients diagnosed with IH. However, the precise mechanisms of bone loss or failure of adequate bone mass gain are still unknown. The largest accumulation of bone mass occurs during childhood and adolescence, peaking atthe end of the second decade of life. This accumulation should occur without interference to achieve the peak of optimal bone mass. Any interference may be a risk factor for the reduction of bone mass with increased risk of fractures in adulthood. This review will address the pathogenesis of IH and its consequence in bone mass.展开更多
N6-methyladenosine(m^(6)A)is the most prevalent modification in the eukaryotic transcriptome and has a wide range of functions in coding and noncoding RNAs.It affects the fate of the modified RNA,including its stabili...N6-methyladenosine(m^(6)A)is the most prevalent modification in the eukaryotic transcriptome and has a wide range of functions in coding and noncoding RNAs.It affects the fate of the modified RNA,including its stability,splicing,and translation,and plays an important role in post-transcriptional regulation.Bones play a key role in supporting and pro-tecting muscles and other organs,facilitating the movement of the organism,ensuring blood production,etc.Bone diseases such as osteoarthritis,osteoporosis,and bone tumors are serious public health problems.The processes of bone development and osteogenic differen-tiation require the precise regulation of gene expression through epigenetic mechanisms including histone,DNA,and RNA modifications.As a reversible dynamic epigenetic mark,m^(6)A modifications affect nearly every important biological process,cellular component,and molecular function,including skeletal development and homeostasis.In recent years,studies have shown that m^(6)A modification is involved in osteogenesis and bone-related diseases.In this review,we summarized the proteins involved in RNA m^(6)A modification and the latest progress in elucidating the regulatory role of m^(6)A modification in bone formation and stem cell direc-tional differentiation.We also discussed the pathological roles and potential molecular mech-anisms of m^(6)A modification in bone-related diseases like osteoporosis and osteosarcoma and suggested potential areas for new strategies that could be used to prevent or treat bone de-fects and bone diseases.展开更多
The ways in which epigenetic modifications fix the effects of early environmental events,ensuring sustained responses to transient stimuli,which result in modified gene expression patterns and phenotypes later in life...The ways in which epigenetic modifications fix the effects of early environmental events,ensuring sustained responses to transient stimuli,which result in modified gene expression patterns and phenotypes later in life,is a topic of considerable interest.This review focuses on recently discovered mechanisms and calls into question prevailing views about the dynamics,position and functions of epigenetic marks.Most epigenetic studies have addressed the long-term effects on a small number of epigenetic marks,at the global or individual gene level,of environmental stressors in humans and animal models.In parallel,increasing numbers of studies based on high-throughput technologies and focusing on humans and mice have revealed additional complexity in epigenetic processes,by highlighting the importance of crosstalk between the different epigenetic marks.A number of studies focusing on the developmental origin of health and disease and metabolic programming have identified links between early nutrition,epigenetic processes and long-term illness.The existence of a self-propagating epigenetic cycle has been demonstrated.Moreover,recent studies demonstrate an obvious sexual dimorphism both for programming trajectories and in response to the same environmental insult.Despite recent progress,we are still far from understanding how,when and where environmental stressors disturb key epigenetic mechanisms.Thus,identifying the original key marks and their changes throughout development during an individual's lifetime or over several generations remains a challenging issue.展开更多
The developmental origins of health and diseases(DOHaD)is a concept stating that adverse intrauterine environments contribute to the health risks of offspring.Since the theory emerged more than 30 years ago,many epide...The developmental origins of health and diseases(DOHaD)is a concept stating that adverse intrauterine environments contribute to the health risks of offspring.Since the theory emerged more than 30 years ago,many epidemiological and animal studies have confirmed that in utero exposure to environmental insults,including hyperglycemia and chemicals,increased the risk of developing noncommunicable diseases(NCDs).These NCDs include metabolic syndrome,type 2 diabetes,and complications such as diabetic cardiomyopathy.Studying the effects of different environmental insults on early embryo development would aid in understanding the underlying mechanisms by which these insults promote NCD development.Embryonic stem cells(ESCs)have also been utilized by researchers to study the DOHaD.ESCs have pluripotent characteristics and can be differentiated into almost every cell lineage;therefore,they are excellent in vitro models for studying early developmental events.More importantly,human ESCs(hESCs)are the best alternative to human embryos for research because of ethical concerns.In this review,we will discuss different maternal conditions associated with DOHaD,focusing on the complications of maternal diabetes.Next,we will review the differentiation protocols developed to generate different cell lineages from hESCs.Additionally,we will review how hESCs are utilized as a model for research into the DOHaD.The effects of environmental insults on hESC differentiation and the possible involvement of epigenetic regulation will be discussed.展开更多
Metal-organic frameworks(MOFs), a class of hybrid materials, consist of organic linkers and bridging metal ions or clusters. Their tunable pore sizes, large surface area, good biocompatibility, structural variability ...Metal-organic frameworks(MOFs), a class of hybrid materials, consist of organic linkers and bridging metal ions or clusters. Their tunable pore sizes, large surface area, good biocompatibility, structural variability in combination with materials and chemicals, and osteogenic effects provide potential approaches for bone tissue engineering and bone diseases. And there are more and more research on MOFs in the field of osteogenesis in recent years. This review presents an overall summary of the application in the bone tissue engineering and bone diseases of MOFs and their composites, starting with the synthesis of MOFs, which discusses the advantages and disadvantages of different syntheses. Then, the biological functions of MOFs are discussed, which are the basics of MOFs applied in the organism. Importantly,mechanisms and abundant applications of MOFs are detailed in the bone tissue engineering and bone diseases. Finally, some prospects of MOFs are discussed, for instance, exploring whether MOFs can be used to treat other bone diseases.展开更多
Oxidative stress has been strongly associated with Parkinson disease (PD) aetiology. We investigated the effects of blueberry extract (BBE) supplementation on α-synuclein induced phenotypes in a Drosophila melanogast...Oxidative stress has been strongly associated with Parkinson disease (PD) aetiology. We investigated the effects of blueberry extract (BBE) supplementation on α-synuclein induced phenotypes in a Drosophila melanogaster model of PD. Enhanced α-synuclein expression in D. melanogaster dopaminergic (DA) neurons can reduce lifespan and we have performed longevity assays to measure the effects of BBE on D. melanogaster survival. Flies expressing α-synuclein in their DA neurons fed BBE had up to an 8 day, or 15%, greater median lifespan than those fed a standard control diet. In addition, BBE improved α-synuclein-induced developmental defects in the Drosophila eye. Our biometric analyses revealed that individuals fed BBE had less atypical ommatidia as well as an increased number of mechanosensory bristle cells than those fed a control diet. We propose that BBE, rich in naturally occurring antioxidants, promotes the survival of neurons in tissues with increased levels of α-synuclein through a protective cell survival mechanism.展开更多
Given that the liver is involved in many metabolic mechanisms,it is not surprising that chronic liver disease(CLD)could have numerous complications.Secondary osteoporosis and increased bone fragility are frequently ov...Given that the liver is involved in many metabolic mechanisms,it is not surprising that chronic liver disease(CLD)could have numerous complications.Secondary osteoporosis and increased bone fragility are frequently overlooked complications in CLD patients.Previous studies implied that up to one-third of these individuals meet diagnostic criteria for osteopenia or osteoporosis.Recent publications indicated that CLD-induced bone fragility depends on the etiology,duration,and stage of liver disease.Therefore,the increased fracture risk in CLD patients puts a severe socioeconomic burden on the health system and urgently requires more effective prevention,diagnosis,and treatment measures.The pathogenesis of CLD-induced bone loss is multifactorial and still insufficiently understood,especially considering the relative impact of increased bone resorption and reduced bone formation in these individuals.It is essential to note that inconsistent findings regarding bone mineral density measurement were previously reported in these individuals.Bone mineral density is widely used as the“golden standard”in the clinical assessment of bone fragility although it is not adequate to predict individual fracture risk.Therefore,microscale bone alterations(bone microstructure,mechanical properties,and cellular indices)were analyzed in CLD individuals.These studies further support the thesis that bone strength could be compromised in CLD individuals,implying that an individualized approach to fracture risk assessment and subsequent therapy is necessary for CLD patients.However,more well-designed studies are required to solve the bone fragility puzzle in CLD patients.展开更多
Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanis...Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.展开更多
Since 1990,China has made considerable progress in resolving the problem of“treatment difficulty”of cardiovascular diseases(CVD).The prevalent unhealthy lifestyle among Chinese residents has exposed a massive propor...Since 1990,China has made considerable progress in resolving the problem of“treatment difficulty”of cardiovascular diseases(CVD).The prevalent unhealthy lifestyle among Chinese residents has exposed a massive proportion of the population to CVD risk factors,and this situation is further worsened due to the accelerated aging population in China.CVD remains one of the greatest threats to the health of Chinese residents.In terms of the proportions of disease mortality among urban and rural residents in China,CVD has persistently ranked first.In 2021,CVD accounted for 48.98%and 47.35%of deaths in rural and urban areas,respectively.Two out of every five deaths can be attributed to CVD.To implement a national policy“focusing on the primary health institute and emphasizing prevention”and truly achieve a shift of CVD prevention and treatment from hospitals to communities,the National Center for Cardiovascular Diseases has organized experts from relevant fields across China to compile the“Report on Cardiovascular Health and Diseases in China”annually since 2005.The 2024 report is established based on representative,published,and high-quality big-data research results from cross-sectional and cohort population epidemiological surveys,randomized controlled clinical trials,large sample registry studies,and typical community prevention and treatment cases,along with data from some projects undertaken by the National Center for Cardiovascular Diseases.These firsthand data not only enrich the content of the current report but also provide a more timely and comprehensive reflection of the status of CVD prevention and treatment in China.展开更多
Apoptosis is crucial for tissue homeostasis and organ development.In bone,apoptosis is recognized to be a main fate of osteoblasts,yet the relevance of this process remains underexplored.Using our murine model with in...Apoptosis is crucial for tissue homeostasis and organ development.In bone,apoptosis is recognized to be a main fate of osteoblasts,yet the relevance of this process remains underexplored.Using our murine model with inducible Caspase 9,the enzyme that initiates intrinsic apoptosis,we triggered apoptosis in a proportion of mature osteocalcin(OCN^(+))osteoblasts and investigated the impact on postnatal bone development.展开更多
文摘BACKGROUND Bone disease is an under-recognized cause of morbidity in chronic pancreatitis(CP).Over the past decade,publications of original studies on bone disease in CP has warranted synthesis of the evidence to ascertain the true burden of the problem.AIM To quantify the prevalence of osteopenia,osteoporosis,and fragility fractures in CP patients and investigate the associated clinical features and outcomes.METHODS A systematic search identified studies investigating bone disease in CP patients from Cochrane Library,Embase,Google Scholar,Ovid Medline,PubMed,Scopus,and Web of Science,from inception until October 2022.The outcomes included prevalence of osteopenia,osteoporosis,and fragility fractures,which were metaanalyzed using a random-effects model and underwent metaregression to delineate association with baseline clinical features.RESULTS Twenty-one studies were included for systematic review and 18 studies were included for meta-analysis.The pooled prevalence of osteopenia and osteoporosis in CP patients was 41.2%(95%CI:35.2%-47.3%)and 20.9%(95%CI:14.9%-27.6%),respectively.The pooled prevalence of fragility fractures described among CP was 5.9%(95%CI:3.9%-8.4%).Metaregression revealed significant association of pancreatic enzyme replacement therapy(PERT)use with prevalence of osteoporosis[coefficient:1.7(95%CI:0.6-2.8);P<0.0001].We observed no associations with mean age,sex distribution,body mass index,alcohol or smoking exposure,diabetes with prevalence of osteopenia,osteoporosis or fragility fractures.Paucity of data on systemic inflammation,CP severity,and bone mineralization parameters precluded a formal metaanalysis.CONCLUSION This meta-analysis confirms significant bone disease in patients with CP.Other than PERT use,we observed no patient or study-specific factor to be significantly associated with CP-related bone disease.Further studies are needed to identify confounders,at-risk population,and to understand the mechanisms of CP-related bone disease and the implications of treatment response.
文摘Substantial evidence exists that in addition to the well-known complications of diabetes, increased fracture risk is an important morbidity. This risk is probably due to altered bone properties in diabetes. Circulating biochemical markers of bone turnover have been found to be decreased in type 2 diabetes （T2D） and may be predictive of fractures independently of bone mineral density （BMD）. Serum sclerostin levels have been found to be increased in T2D and appear to be predictive of fracture risk independent of BMD. Bone imaging technologies, including trabecular bone score （TBS） and quantitative CT testing have revealed differences in diabetic bone as compared to non-diabetic individuals. Specifically, high resolution peripheral quantitative CT （HRpQCT） imaging has demonstrated increased cortical porosity in diabetic postmenopausal women. Other factors such as bone marrow fat saturation and advanced glycation endproduct （AGE） accumulation might also relate to bone cell function and fracture risk in diabetes. These data have increased our understanding of how T2D adversely impacts both bone metabolism and fracture risk.
基金the National Natural Science Foundation of China,No.81870743 and No.81771048.
文摘Bone is a complex tissue that undergoes constant remodeling to maintain homeostasis,which requires coordinated multilineage differentiation and proper proliferation of mesenchymal stromal cells(MSCs).Mounting evidence indicates that a disturbance of bone homeostasis can trigger degenerative bone diseases,including osteoporosis and osteoarthritis.In addition to conventional genetic modifications,epigenetic modifications(i.e.,DNA methylation,histone modifications,and the expression of noncoding RNAs)are considered to be contributing factors that affect bone homeostasis.Long noncoding RNAs(lncRNAs)were previously regarded as‘transcriptional noise’with no biological functions.However,substantial evidence suggests that lncRNAs have roles in the epigenetic regulation of biological processes in MSCs and related diseases.In this review,we summarized the interactions between lncRNAs and epigenetic modifiers associated with osteo-/adipogenic differentiation of MSCs and the pathogenesis of degenerative bone diseases and highlighted promising lncRNA-based diagnostic and therapeutic targets for bone diseases.
文摘Metastatic bone disease of the distal extremities,also known as acrometastasis,is very rare.Thus,there is very limited information regarding the clinical manifestations and methods of surgical treatment.The current available literature shows that acrometastases are often encountered in the context of advanced disease and are thus associated with poor patient survival.As metastatic bone disease is generally uncurable,the goal of surgical treatment is to provide the patient with good function with as few complications as possible.In this article,we discuss the clinical manifestation of acrometastases,the methods of surgical intervention,and the expected clinical outcome.Non-surgically managed pathological fractures generally remain ununited;therefore,conservative treatment is reserved for patients with poor general condition or dismal prognosis.The current evidence suggests that in lesions of the lower arm and leg,osteosynthesis(plate and screw fixation or intramedullary nail)is the most common method of reconstruction,whereas local excision or amputation are more commonly used in cases of more distal lesions(such as ankle,foot and hand).Following surgery most patients receive adjuvant radiotherapy,even though its role is poorly documented.Close collaboration between orthopedic surgeons and medical oncologists is necessary to improve patient care and treatment outcome.Further studies are needed in order to provide stronger clinical evidence and improve decision-making,in an effort to optimize the patients’quality of life and avoid the need for revision surgery.
基金Supported by the Municipal Natural Science Foundation of Beijing of China,No.7192071.
文摘BACKGROUND The neutrophil-lymphocyte ratio(NLR)is often used to predict a poor prognosis in patients with tumors.This study investigated the preoperative peripheral blood NLR in predicting postoperative survival(POS)in patients with multiple myeloma bone disease(MMBD).AIM To evaluate whether NLR can be used to predict the prognosis of MMBD patients after surgery.METHODS The clinical data of 82 MMBD patients who underwent surgical treatments in Beijing Chao-yang Hospital were collected.The NLR was obtained from the absolute number of neutrophils and lymphocytes,calculated by the number of neutrophils and divided by the number of lymphocytes.The peripheral blood lymphocyte percentage was used as the major marker to analyze the change in characteristics of the immune statuses of multiple myeloma patients.RESULTS The NLR cut-off values of NLR≥3 patients and NLR≥4 patients were significantly correlated with POS.The 3-and 5-year cumulative survival rates of the high NLR group(NLR≥3 patients)were 19.1%and 0.0%,respectively,which were lower than those of the low NLR group(NLR<3 patients)(67.2%and 48.3%)(P=0.000).In the high NLR group,POS(14.86±14.28)was significantly shorter than that in the low NLR group(32.68±21.76).Univariate analysis showed that the lymphocyte percentage 1 wk after the operation(19.33±9.08)was significantly lower than that before the operation(25.72±11.02).Survival analysis showed that postoperative chemotherapy,preoperative performance status and preoperative peripheral blood NLR≥3 were independent risk factors for POS.CONCLUSION The preoperative peripheral blood NLR can predict POS in MMBD patients.MMBD patients with a high preoperative NLR(NLR≥3)showed poor prognosis.
文摘This is a retrospective analysis of long-term efficacy of parathyroidectomy on hyperparathyroid bone disease. The clinical manifestations, bone structure, and bone mineral density in 16 patients averaged 5.1 (1. 0-10. 5) years after parathyroidectomy were assessed. The results showed that although the bone disease could be markedly relieved after surgery, yet at terminal point of follow-up, 10/16 cases (62. 5% ) got incomplete recovery of bone disease, the ratio of incomplete recovery in Y1 group with severe bone disease was higher than that of Y2 group with mild bone disease (P <0. 05). The concentrations of serum BGP and morning void urine pyridinoline were within the refer ence ranges of young and middle aged controls. These imply that the osteoblastic and osteoclastic activities had reached a balancing state. The results suggested that hyperparathyroid patients should be operated on as early as possible, and intensively followed up after operation. subsequent therapy should be given to patients with incomplete recovery of bone disease.
文摘Vanishing bone disease(Gorham-Stout syndrome) is a rare entity of unknown etiology, characterized by de struction of osseous matrix and proliferation of vascula structures, resulting in destruction and absorption o bone. Despite the extensive investigation of the patho genetic mechanisms of the disease, its etiology hasn'been clarified and several theories exist. The syndrome can affect one or multiple bones of the patient, includ ing the skull, the upper and lower extremities, the spine and pelvis. The clinical presentation of a patient suffer ing from vanishing bone disease includes, pain, func tional impairment and swelling of the affected region although asymptomatic cases have been reported, as well as cases in which the diagnosis was made after a pathologic fracture. In this short review we summarize the theories regarding the etiology as well as the clini cal presentation, the diagnostic approach and treat ment options of this rare disease.
基金Supported by Grants from the Spanish Ministry of Economíay Competitividad-Instituto de Salud CarlosⅢ,No.PI12/02591European Funds for Regional Development+3 种基金the Spanish Health Thematic Networks of Cooperative Research in Cancer,No.RTICC RD12/0036/0058Cellular Therapy,No.TerCelRD12/0019/0001,group 8the Network of Centers for Regenera-tive Medicine and Cellular Therapy from Castilla y Leónthe Spanish Society of Hematology and Hemotherapy(to Garcia-Gomez A)
文摘Multiple myeloma is a hematological malignancy inwhich clonal plasma cells proliferate and accumulate within the bone marrow. The presence of osteolytic le-sions due to increased osteoclast(OC) activity and sup-pressed osteoblast(OB) function is characteristic of the disease. The bone marrow mesenchymal stromal cells(MSCs) play a critical role in multiple myeloma patho-physiology, greatly promoting the growth, survival, drug resistance and migration of myeloma cells. Here, we specifically discuss on the relative contribution of MSCs to the pathophysiology of osteolytic lesions in light of the current knowledge of the biology of my-eloma bone disease(MBD), together with the reported genomic, functional and gene expression differences between MSCs derived from myeloma patients(pMSCs) and their healthy counterparts(dMSCs). Being MSCs the progenitors of OBs, pMSCs primarily contribute to the pathogenesis of MBD because of their reduced osteogenic potential consequence of multiple OB inhibi-tory factors and direct interactions with myeloma cells in the bone marrow. Importantly, pMSCs also readily contribute to MBD by promoting OC formation and ac-tivity at various levels(i.e., increasing RANKL to OPG expression, augmenting secretion of activin A, uncou-pling ephrinB2-EphB4 signaling, and through augment-ed production of Wnt5a), thus further contributing to OB/OC uncoupling in osteolytic lesions. In this review, we also look over main signaling pathways involved in the osteogenic differentiation of MSCs and/or OB activity, highlighting amenable therapeutic targets; in parallel, the reported activity of bone-anabolic agents(at preclinical or clinical stage) targeting those signaling pathways is commented.
文摘Bone disease(osteopenia or osteoporosis)is a highly prevalent condition in society and presents a tremendous,preventable public health burden.Screening procedures,such as,dual-energy X-ray absorptiometry scans,have allowed early identification and intervention to improve bone health,and reduce the risk of osteoporotic fractures,which carry significant morbidity and mortality.The association of bone disease has been recognized in several diseases of the gastrointestinal tract,resulting in established guidelines for screening in patients with malabsorptive disorders such as inflammatory bowel disease and celiac disease.Increasingly,the risk of bone disease has been recognized in patients with chronic pancreatitis(CP),who share similar risk factors as patients with other high gastrointestinal disorders.As a result,there have been a number of studies examining the prevalence and risks of bone disease and fractures in patients with CP.This review aims to summarize the recent literature and current recommendations related to bone disease in CP.
基金supported by grants from the Irish Research Council(R13702 and R15897SVH/AS/G’OK)+3 种基金the Health Research Board of Ireland(HRA/2009/127GO’K/AS)Science Foundation Ireland(10/RFP/NES2786GO’K)
文摘Neuroprotection and neuroregeneration are two of the most promising disease-modifying ther- apies for the incurable and widespread Parkinson＇s disease. In Parkinson＇s disease, progressive degeneration of nigrostriatal dopaminergic neurons causes debilitating motor symptoms. Neurotrophic factors play important regulatory roles in the development, survival and maintenance of specific neuronal populations. These factors have the potential to slow down, halt or reverse the loss of nigrostriatal dopaminergic neurons in Parkinsoffs disease. Several neurotrophic fac- tors have been investigated in this regard. This review article discusses the neurodevelopmental roles and therapeutic potential of three dopaminergic neurotrophic factors： glial cell line-derived neurotrophic factor, neurturin and growth/differentiation factor 5.
文摘Idiopathic hypercalciuria （IH） is the leading metabolic risk factor for urolithiasis and affects all age groups without gender or race predominance. IH has a high morbidity with or without lithiasis and reduced bone mineral density （BMD）, as described previously in pe-diatric patients as well as in adults. The pathogenesis of IH is complex and not completely understood, given that urinary excretion of calcium is the end result of an interplay between three organs （gut, bone and kidney）, which is further orchestrated by hormones, such as 1,25 dihydroxyvitamin D, parathyroid hormone, calcitonin and fosfatonins （i.e., fbroblast growth-factor-23）. Usu-ally, a primary defect in one organ induces compensa-tory mechanisms in the remaining two organs, such as increased absorption of calcium in the gut secondary toa primary renal loss. Thus, IH is a systemic abnormality of calcium homeostasis with changes in cellular trans-port of this ion in intestines, kidneys and bones. Re-duced BMD has been demonstrated in pediatric patients diagnosed with IH. However, the precise mechanisms of bone loss or failure of adequate bone mass gain are still unknown. The largest accumulation of bone mass occurs during childhood and adolescence, peaking atthe end of the second decade of life. This accumulation should occur without interference to achieve the peak of optimal bone mass. Any interference may be a risk factor for the reduction of bone mass with increased risk of fractures in adulthood. This review will address the pathogenesis of IH and its consequence in bone mass.
基金supported by the National Natural Science Foundation of China(No.81870743,82170934)the Sichuan Science and Technology Program(China)(No.2022YFG0280)。
文摘N6-methyladenosine(m^(6)A)is the most prevalent modification in the eukaryotic transcriptome and has a wide range of functions in coding and noncoding RNAs.It affects the fate of the modified RNA,including its stability,splicing,and translation,and plays an important role in post-transcriptional regulation.Bones play a key role in supporting and pro-tecting muscles and other organs,facilitating the movement of the organism,ensuring blood production,etc.Bone diseases such as osteoarthritis,osteoporosis,and bone tumors are serious public health problems.The processes of bone development and osteogenic differen-tiation require the precise regulation of gene expression through epigenetic mechanisms including histone,DNA,and RNA modifications.As a reversible dynamic epigenetic mark,m^(6)A modifications affect nearly every important biological process,cellular component,and molecular function,including skeletal development and homeostasis.In recent years,studies have shown that m^(6)A modification is involved in osteogenesis and bone-related diseases.In this review,we summarized the proteins involved in RNA m^(6)A modification and the latest progress in elucidating the regulatory role of m^(6)A modification in bone formation and stem cell direc-tional differentiation.We also discussed the pathological roles and potential molecular mech-anisms of m^(6)A modification in bone-related diseases like osteoporosis and osteosarcoma and suggested potential areas for new strategies that could be used to prevent or treat bone de-fects and bone diseases.
基金Supported by Grants from INRA,INSERM (ATC-Nutrition,PRNH)Association Franaise des Diabétiques+3 种基金the Institut Benjamin Delessertthe Fondation Coeur et Artères (FCA N° 05-T4)the Agence Nationale pour la Recherche (ANR 06-PNRA-022-01)Contrat Cadre d’Aide au Projet d’Innova-tion Stratégique Industrielle "IT-Diab"OSEO-ISI (ISI IT-DIAB-18/12/2008)
文摘The ways in which epigenetic modifications fix the effects of early environmental events,ensuring sustained responses to transient stimuli,which result in modified gene expression patterns and phenotypes later in life,is a topic of considerable interest.This review focuses on recently discovered mechanisms and calls into question prevailing views about the dynamics,position and functions of epigenetic marks.Most epigenetic studies have addressed the long-term effects on a small number of epigenetic marks,at the global or individual gene level,of environmental stressors in humans and animal models.In parallel,increasing numbers of studies based on high-throughput technologies and focusing on humans and mice have revealed additional complexity in epigenetic processes,by highlighting the importance of crosstalk between the different epigenetic marks.A number of studies focusing on the developmental origin of health and disease and metabolic programming have identified links between early nutrition,epigenetic processes and long-term illness.The existence of a self-propagating epigenetic cycle has been demonstrated.Moreover,recent studies demonstrate an obvious sexual dimorphism both for programming trajectories and in response to the same environmental insult.Despite recent progress,we are still far from understanding how,when and where environmental stressors disturb key epigenetic mechanisms.Thus,identifying the original key marks and their changes throughout development during an individual's lifetime or over several generations remains a challenging issue.
文摘The developmental origins of health and diseases(DOHaD)is a concept stating that adverse intrauterine environments contribute to the health risks of offspring.Since the theory emerged more than 30 years ago,many epidemiological and animal studies have confirmed that in utero exposure to environmental insults,including hyperglycemia and chemicals,increased the risk of developing noncommunicable diseases(NCDs).These NCDs include metabolic syndrome,type 2 diabetes,and complications such as diabetic cardiomyopathy.Studying the effects of different environmental insults on early embryo development would aid in understanding the underlying mechanisms by which these insults promote NCD development.Embryonic stem cells(ESCs)have also been utilized by researchers to study the DOHaD.ESCs have pluripotent characteristics and can be differentiated into almost every cell lineage;therefore,they are excellent in vitro models for studying early developmental events.More importantly,human ESCs(hESCs)are the best alternative to human embryos for research because of ethical concerns.In this review,we will discuss different maternal conditions associated with DOHaD,focusing on the complications of maternal diabetes.Next,we will review the differentiation protocols developed to generate different cell lineages from hESCs.Additionally,we will review how hESCs are utilized as a model for research into the DOHaD.The effects of environmental insults on hESC differentiation and the possible involvement of epigenetic regulation will be discussed.
基金supported by the National Natural Science Foundation of China (Nos. 82071164 and 82271016)Key Research Program of Sichuan Science and Technology Department (No. 2021YFS0052)。
文摘Metal-organic frameworks(MOFs), a class of hybrid materials, consist of organic linkers and bridging metal ions or clusters. Their tunable pore sizes, large surface area, good biocompatibility, structural variability in combination with materials and chemicals, and osteogenic effects provide potential approaches for bone tissue engineering and bone diseases. And there are more and more research on MOFs in the field of osteogenesis in recent years. This review presents an overall summary of the application in the bone tissue engineering and bone diseases of MOFs and their composites, starting with the synthesis of MOFs, which discusses the advantages and disadvantages of different syntheses. Then, the biological functions of MOFs are discussed, which are the basics of MOFs applied in the organism. Importantly,mechanisms and abundant applications of MOFs are detailed in the bone tissue engineering and bone diseases. Finally, some prospects of MOFs are discussed, for instance, exploring whether MOFs can be used to treat other bone diseases.
文摘Oxidative stress has been strongly associated with Parkinson disease (PD) aetiology. We investigated the effects of blueberry extract (BBE) supplementation on α-synuclein induced phenotypes in a Drosophila melanogaster model of PD. Enhanced α-synuclein expression in D. melanogaster dopaminergic (DA) neurons can reduce lifespan and we have performed longevity assays to measure the effects of BBE on D. melanogaster survival. Flies expressing α-synuclein in their DA neurons fed BBE had up to an 8 day, or 15%, greater median lifespan than those fed a standard control diet. In addition, BBE improved α-synuclein-induced developmental defects in the Drosophila eye. Our biometric analyses revealed that individuals fed BBE had less atypical ommatidia as well as an increased number of mechanosensory bristle cells than those fed a control diet. We propose that BBE, rich in naturally occurring antioxidants, promotes the survival of neurons in tissues with increased levels of α-synuclein through a protective cell survival mechanism.
文摘Given that the liver is involved in many metabolic mechanisms,it is not surprising that chronic liver disease(CLD)could have numerous complications.Secondary osteoporosis and increased bone fragility are frequently overlooked complications in CLD patients.Previous studies implied that up to one-third of these individuals meet diagnostic criteria for osteopenia or osteoporosis.Recent publications indicated that CLD-induced bone fragility depends on the etiology,duration,and stage of liver disease.Therefore,the increased fracture risk in CLD patients puts a severe socioeconomic burden on the health system and urgently requires more effective prevention,diagnosis,and treatment measures.The pathogenesis of CLD-induced bone loss is multifactorial and still insufficiently understood,especially considering the relative impact of increased bone resorption and reduced bone formation in these individuals.It is essential to note that inconsistent findings regarding bone mineral density measurement were previously reported in these individuals.Bone mineral density is widely used as the“golden standard”in the clinical assessment of bone fragility although it is not adequate to predict individual fracture risk.Therefore,microscale bone alterations(bone microstructure,mechanical properties,and cellular indices)were analyzed in CLD individuals.These studies further support the thesis that bone strength could be compromised in CLD individuals,implying that an individualized approach to fracture risk assessment and subsequent therapy is necessary for CLD patients.However,more well-designed studies are required to solve the bone fragility puzzle in CLD patients.
基金financially supported by Shenzhen Agricultural Development Special Fund(Fishery)Agricultural High-Tech Project([2021]735)the Shenzhen Science and Technology Innovation Commission(KCXFZ20201221173207022)Youth Science Foundation Project(32101936)。
文摘Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.
文摘Since 1990,China has made considerable progress in resolving the problem of“treatment difficulty”of cardiovascular diseases(CVD).The prevalent unhealthy lifestyle among Chinese residents has exposed a massive proportion of the population to CVD risk factors,and this situation is further worsened due to the accelerated aging population in China.CVD remains one of the greatest threats to the health of Chinese residents.In terms of the proportions of disease mortality among urban and rural residents in China,CVD has persistently ranked first.In 2021,CVD accounted for 48.98%and 47.35%of deaths in rural and urban areas,respectively.Two out of every five deaths can be attributed to CVD.To implement a national policy“focusing on the primary health institute and emphasizing prevention”and truly achieve a shift of CVD prevention and treatment from hospitals to communities,the National Center for Cardiovascular Diseases has organized experts from relevant fields across China to compile the“Report on Cardiovascular Health and Diseases in China”annually since 2005.The 2024 report is established based on representative,published,and high-quality big-data research results from cross-sectional and cohort population epidemiological surveys,randomized controlled clinical trials,large sample registry studies,and typical community prevention and treatment cases,along with data from some projects undertaken by the National Center for Cardiovascular Diseases.These firsthand data not only enrich the content of the current report but also provide a more timely and comprehensive reflection of the status of CVD prevention and treatment in China.
基金supported in part by funding from the National Institutes of Health (DK053904,DE022327,AR077539,CA093900,CA046592 and P30 AR069620)National Health and Medical Research Council (APP1143802)Mater Foundation.
文摘Apoptosis is crucial for tissue homeostasis and organ development.In bone,apoptosis is recognized to be a main fate of osteoblasts,yet the relevance of this process remains underexplored.Using our murine model with inducible Caspase 9,the enzyme that initiates intrinsic apoptosis,we triggered apoptosis in a proportion of mature osteocalcin(OCN^(+))osteoblasts and investigated the impact on postnatal bone development.
