The lymphatic vasculature forms an organized network that covers the whole body and is involved in fluid homeostasis,metabolite clearance,and immune surveillance.The recent identification of functional lymphatic vesse...The lymphatic vasculature forms an organized network that covers the whole body and is involved in fluid homeostasis,metabolite clearance,and immune surveillance.The recent identification of functional lymphatic vessels in the meninges of the brain and the spinal cord has provided novel insights into neurophysiology.They emerge as major pathways for fluid exchange.The abundance of immune cells in lymphatic vessels and meninges also suggests that lymphatic vessels are actively involved in neuroimmunity.The lymphatic system,through its role in the clearance of neurotoxic proteins,autoimmune cell infiltration,and the transmission of pro-inflammatory signals,participates in the pathogenesis of a variety of neurological disorders,including neurodegenerative and neuroinflammatory diseases and traumatic injury.Vascular endothelial growth factor C is the master regulator of lymphangiogenesis,a process that is critical for the maintenance of central nervous system homeostasis.In this review,we summarize current knowledge and recent advances relating to the anatomical features and immunological functions of the lymphatic system of the central nervous system and highlight its potential as a therapeutic target for neurological disorders and central nervous system repair.展开更多
Background:Osteopenia has been well documented in adolescent idiopathic scoliosis(AIS).Bone marrow stem cells(BMSCs)are a crucial regulator of bone homeostasis.Our previous study revealed a decreased osteogenic abilit...Background:Osteopenia has been well documented in adolescent idiopathic scoliosis(AIS).Bone marrow stem cells(BMSCs)are a crucial regulator of bone homeostasis.Our previous study revealed a decreased osteogenic ability of BMSCs in AIS-related osteopenia,but the underlying mechanism of this phenomenon remains unclear.Methods:A total of 22 AIS patients and 18 age-matched controls were recruited for this study.Anthropometry and bone mass were measured in all participants.Bone marrow blood was collected for BMSC isolation and culture.Osteogenic and adipogenic induction were performed to observe the differences in the differentiation of BMSCs between the AIS-related osteopenia group and the control group.Furthermore,a total RNA was extracted from isolated BMSCs to perform RNA sequencing and subsequent analysis.Results:A lower osteogenic capacity and increased adipogenic capacity of BMSCs in AIS-related osteopenia were revealed.Differences in mRNA expression levels between the AIS-related osteopenia group and the control group were identified,including differences in the expression of LRRC17,DCLK1,PCDH7,TSPAN5,NHSL2,and CPT1B.Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed several biological processes involved in the regulation of autophagy and mitophagy.The Western blotting results of autophagy markers in BMSCs suggested impaired autophagic activity in BMSCs in the AIS-related osteopenia group.Conclusion:Our study revealed that BMSCs from AIS-related osteopenia patients have lower autophagic activity,which may be related to the lower osteogenic capacity and higher adipogenic capacity of BMSCs and consequently lead to the lower bone mass in AIS patients.展开更多
Background:Congenital scoliosis(CS)is a complex spinal malformation of unknown etiology with abnormal bone metabolism.Fibroblast growth factor 23(FGF23),secreted by osteoblasts and osteocytes,can inhibit bone formatio...Background:Congenital scoliosis(CS)is a complex spinal malformation of unknown etiology with abnormal bone metabolism.Fibroblast growth factor 23(FGF23),secreted by osteoblasts and osteocytes,can inhibit bone formation and mineralization.This research aims to investigate the relationship between CS and FGF23.Methods:We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region.FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured.Receiver operator characteristic(ROC)curve analyses were conducted to evaluate the specificity and sensitivity of FGF23.The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3(FGFr3)/tissue non-specific alkaline phosphatase(TNAP)/osteopontin(OPN)in primary osteoblasts from CS patients(CS-Ob)and controls(CT-Ob)were detected.In addition,the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined.Results:DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins,accompanied by increased mRNA levels.CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography(CT)values compared with controls.The FGF23 mRNA levels were negatively correlated with the CT value of the spine,and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS.Additionally,significantly increased levels of FGF23,FGFr3,OPN,impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob.Moreover,FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels,while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob.Mineralization of CS-Ob was rescued after FGF23 knockdown.Conclusions:Our results suggested increased peripheral blood FGF23 levels,decreased bone mineral density in CS patients,and a good predictive ability of CS by peripheral blood FGF23 levels.FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP/OPN pathway.展开更多
基金supported by the Key Program of the National Natural Science Foundation of ChinaNo.82030071+1 种基金the Science and Technology Major Project of ChangshaNo.kh2103008 (both to JZH)
文摘The lymphatic vasculature forms an organized network that covers the whole body and is involved in fluid homeostasis,metabolite clearance,and immune surveillance.The recent identification of functional lymphatic vessels in the meninges of the brain and the spinal cord has provided novel insights into neurophysiology.They emerge as major pathways for fluid exchange.The abundance of immune cells in lymphatic vessels and meninges also suggests that lymphatic vessels are actively involved in neuroimmunity.The lymphatic system,through its role in the clearance of neurotoxic proteins,autoimmune cell infiltration,and the transmission of pro-inflammatory signals,participates in the pathogenesis of a variety of neurological disorders,including neurodegenerative and neuroinflammatory diseases and traumatic injury.Vascular endothelial growth factor C is the master regulator of lymphangiogenesis,a process that is critical for the maintenance of central nervous system homeostasis.In this review,we summarize current knowledge and recent advances relating to the anatomical features and immunological functions of the lymphatic system of the central nervous system and highlight its potential as a therapeutic target for neurological disorders and central nervous system repair.
基金National Natural Science Foundation of China(No.82072390)Natural Science Foundation of Hunan,China(No.2020JJ4873)
文摘Background:Osteopenia has been well documented in adolescent idiopathic scoliosis(AIS).Bone marrow stem cells(BMSCs)are a crucial regulator of bone homeostasis.Our previous study revealed a decreased osteogenic ability of BMSCs in AIS-related osteopenia,but the underlying mechanism of this phenomenon remains unclear.Methods:A total of 22 AIS patients and 18 age-matched controls were recruited for this study.Anthropometry and bone mass were measured in all participants.Bone marrow blood was collected for BMSC isolation and culture.Osteogenic and adipogenic induction were performed to observe the differences in the differentiation of BMSCs between the AIS-related osteopenia group and the control group.Furthermore,a total RNA was extracted from isolated BMSCs to perform RNA sequencing and subsequent analysis.Results:A lower osteogenic capacity and increased adipogenic capacity of BMSCs in AIS-related osteopenia were revealed.Differences in mRNA expression levels between the AIS-related osteopenia group and the control group were identified,including differences in the expression of LRRC17,DCLK1,PCDH7,TSPAN5,NHSL2,and CPT1B.Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed several biological processes involved in the regulation of autophagy and mitophagy.The Western blotting results of autophagy markers in BMSCs suggested impaired autophagic activity in BMSCs in the AIS-related osteopenia group.Conclusion:Our study revealed that BMSCs from AIS-related osteopenia patients have lower autophagic activity,which may be related to the lower osteogenic capacity and higher adipogenic capacity of BMSCs and consequently lead to the lower bone mass in AIS patients.
基金National Natural Science Foundation of China(No.82072390)Natural Science Foundation of Hunan,China(No.2020JJ4873)
文摘Background:Congenital scoliosis(CS)is a complex spinal malformation of unknown etiology with abnormal bone metabolism.Fibroblast growth factor 23(FGF23),secreted by osteoblasts and osteocytes,can inhibit bone formation and mineralization.This research aims to investigate the relationship between CS and FGF23.Methods:We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region.FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured.Receiver operator characteristic(ROC)curve analyses were conducted to evaluate the specificity and sensitivity of FGF23.The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3(FGFr3)/tissue non-specific alkaline phosphatase(TNAP)/osteopontin(OPN)in primary osteoblasts from CS patients(CS-Ob)and controls(CT-Ob)were detected.In addition,the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined.Results:DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins,accompanied by increased mRNA levels.CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography(CT)values compared with controls.The FGF23 mRNA levels were negatively correlated with the CT value of the spine,and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS.Additionally,significantly increased levels of FGF23,FGFr3,OPN,impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob.Moreover,FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels,while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob.Mineralization of CS-Ob was rescued after FGF23 knockdown.Conclusions:Our results suggested increased peripheral blood FGF23 levels,decreased bone mineral density in CS patients,and a good predictive ability of CS by peripheral blood FGF23 levels.FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP/OPN pathway.
