Systematic bone and muscle loss is a complex metabolic disease,which is frequently linked to gut dysfunction,yet its etiology and treatment remain elusive.While probiotics show promise in managing diseases through mic...Systematic bone and muscle loss is a complex metabolic disease,which is frequently linked to gut dysfunction,yet its etiology and treatment remain elusive.While probiotics show promise in managing diseases through microbiome modulation,their therapeutic impact on gut dysfunction-induced bone and muscle loss remains to be elucidated.Employing dextran sulfate sodium(DSS)-induced gut dysfunction model and wide-spectrum antibiotics(ABX)-treated mice model,our study revealed that gut dysfunction instigates muscle and bone loss,accompanied by microbial imbalances.Importantly,Bifidobacterium animalis subsp.lactis A6(B.lactis A6)administration significantly ameliorated muscle and bone loss by modulating gut microbiota composition and enhancing butyrate-producing bacteria.This intervention effectively restored depleted butyrate levels in serum,muscle,and bone tissues caused by gut dysfunction.Furthermore,butyrate supplementation mitigated musculoskeletal loss by repairing the damaged intestinal barrier and enriching beneficial butyrate-producing bacteria.Importantly,butyrate inhibited the NF-κB pathway activation,and reduced the secretion of corresponding inflammatory factors in T cells.Our study highlights the critical role of dysbiosis in gut dysfunction-induced musculoskeletal loss and underscores the therapeutic potential of B.lactis A6.These discoveries offer new microbiome directions for translational and clinical research,providing promising strategies for preventing and managing musculoskeletal diseases.展开更多
Angiogenesis and osteogenesis are coupled.However,the cellular and molecular regulation of these processes remains to be further investigated.Both tissues have recently been recognized as endocrine organs,which has st...Angiogenesis and osteogenesis are coupled.However,the cellular and molecular regulation of these processes remains to be further investigated.Both tissues have recently been recognized as endocrine organs,which has stimulated research interest in the screening and functional identification of novel paracrine factors from both tissues.This review aims to elaborate on the novelty and significance of endocrine regulatory loops between bone and the vasculature.In addition,research progress related to the bone vasculature,vessel-related skeletal diseases,pathological conditions,and angiogenesis-targeted therapeutic strategies are also summarized.With respect to future perspectives,new techniques such as single-cell sequencing,which can be used to show the cellular diversity and plasticity of both tissues,are facilitating progress in this field.Moreover,extracellular vesicle-mediated nuclear acid communication deserves further investigation.In conclusion,a deeper understanding of the cellular and molecular regulation of angiogenesis and osteogenesis coupling may offer an opportunity to identify new therapeutic targets.展开更多
Regular physical activity is widely recognized for reducing the risk of various disorders,with skeletal muscles playing a key role by releasing biomolecules that benefit multiple organs and tissues.However,many indivi...Regular physical activity is widely recognized for reducing the risk of various disorders,with skeletal muscles playing a key role by releasing biomolecules that benefit multiple organs and tissues.However,many individuals,particularly the elderly and those with clinical conditions,are unable to engage in physical exercise,necessitating alternative strategies to stimulate muscle cells to secrete beneficial biomolecules.Histone acetylation and deacetylation significantly influence exercise-induced gene expression,suggesting that targeting histone deacetylases(HDACs)could mimic some exercise responses.In this study,we explored the effects of the HDAC inhibitor Trichostatin A(TSA)on human skeletal muscle myoblasts(HSMMs).Our findings showed that TSA-induced hyperacetylation enhanced myotube fusion and increased the secretion of extracellular vesicles(EVs)enriched with miR-873-3p.These TSA-EVs promoted osteogenic differentiation in human bone marrow mesenchymal stem cells(hBMSCs)by targeting H2 calponin(CNN2).In vivo,systemic administration of TSA-EVs to osteoporosis mice resulted in significant improvements in bone mass.Moreover,TSA-EVs mimicked the osteogenic benefits of exercise-induced EVs,suggesting that HDAC inhibition can replicate exercise-induced bone health benefits.These results demonstrate the potential of TSA-induced muscle-derived EVs as a therapeutic strategy to enhance bone formation and prevent osteoporosis,particularly for individuals unable to exercise.Given the FDA-approved status of various HDAC inhibitors,this approach holds significant promise for rapid clinical translation in osteoporosis treatment.展开更多
基金supported by funding from the National Natural Science Foundation of China(82272478,82002330,82202728)the National Key R&D Program of China(No.2022YFF1100100)the Natural Science Foundation of Beijing(L222086).
文摘Systematic bone and muscle loss is a complex metabolic disease,which is frequently linked to gut dysfunction,yet its etiology and treatment remain elusive.While probiotics show promise in managing diseases through microbiome modulation,their therapeutic impact on gut dysfunction-induced bone and muscle loss remains to be elucidated.Employing dextran sulfate sodium(DSS)-induced gut dysfunction model and wide-spectrum antibiotics(ABX)-treated mice model,our study revealed that gut dysfunction instigates muscle and bone loss,accompanied by microbial imbalances.Importantly,Bifidobacterium animalis subsp.lactis A6(B.lactis A6)administration significantly ameliorated muscle and bone loss by modulating gut microbiota composition and enhancing butyrate-producing bacteria.This intervention effectively restored depleted butyrate levels in serum,muscle,and bone tissues caused by gut dysfunction.Furthermore,butyrate supplementation mitigated musculoskeletal loss by repairing the damaged intestinal barrier and enriching beneficial butyrate-producing bacteria.Importantly,butyrate inhibited the NF-κB pathway activation,and reduced the secretion of corresponding inflammatory factors in T cells.Our study highlights the critical role of dysbiosis in gut dysfunction-induced musculoskeletal loss and underscores the therapeutic potential of B.lactis A6.These discoveries offer new microbiome directions for translational and clinical research,providing promising strategies for preventing and managing musculoskeletal diseases.
基金funded by the National Natural Science Foundation of China(81972102,81772369,81972115,82002330 and 81702176).
文摘Angiogenesis and osteogenesis are coupled.However,the cellular and molecular regulation of these processes remains to be further investigated.Both tissues have recently been recognized as endocrine organs,which has stimulated research interest in the screening and functional identification of novel paracrine factors from both tissues.This review aims to elaborate on the novelty and significance of endocrine regulatory loops between bone and the vasculature.In addition,research progress related to the bone vasculature,vessel-related skeletal diseases,pathological conditions,and angiogenesis-targeted therapeutic strategies are also summarized.With respect to future perspectives,new techniques such as single-cell sequencing,which can be used to show the cellular diversity and plasticity of both tissues,are facilitating progress in this field.Moreover,extracellular vesicle-mediated nuclear acid communication deserves further investigation.In conclusion,a deeper understanding of the cellular and molecular regulation of angiogenesis and osteogenesis coupling may offer an opportunity to identify new therapeutic targets.
基金National Natural Science Foundation of China(82002330,81972115,82202728)National Key Research and Development Program of China(2022YFC2504300)Beijing Municipal Natural Science Foundation(2022HQ27).
文摘Regular physical activity is widely recognized for reducing the risk of various disorders,with skeletal muscles playing a key role by releasing biomolecules that benefit multiple organs and tissues.However,many individuals,particularly the elderly and those with clinical conditions,are unable to engage in physical exercise,necessitating alternative strategies to stimulate muscle cells to secrete beneficial biomolecules.Histone acetylation and deacetylation significantly influence exercise-induced gene expression,suggesting that targeting histone deacetylases(HDACs)could mimic some exercise responses.In this study,we explored the effects of the HDAC inhibitor Trichostatin A(TSA)on human skeletal muscle myoblasts(HSMMs).Our findings showed that TSA-induced hyperacetylation enhanced myotube fusion and increased the secretion of extracellular vesicles(EVs)enriched with miR-873-3p.These TSA-EVs promoted osteogenic differentiation in human bone marrow mesenchymal stem cells(hBMSCs)by targeting H2 calponin(CNN2).In vivo,systemic administration of TSA-EVs to osteoporosis mice resulted in significant improvements in bone mass.Moreover,TSA-EVs mimicked the osteogenic benefits of exercise-induced EVs,suggesting that HDAC inhibition can replicate exercise-induced bone health benefits.These results demonstrate the potential of TSA-induced muscle-derived EVs as a therapeutic strategy to enhance bone formation and prevent osteoporosis,particularly for individuals unable to exercise.Given the FDA-approved status of various HDAC inhibitors,this approach holds significant promise for rapid clinical translation in osteoporosis treatment.
