Non-healing fractures,a global health concern arising from trauma,osteoporosis,and tumours,can lead to severe disabilities.Adenosine,integral to cellular energy metabolism,gains prominence in bone regeneration via ade...Non-healing fractures,a global health concern arising from trauma,osteoporosis,and tumours,can lead to severe disabilities.Adenosine,integral to cellular energy metabolism,gains prominence in bone regeneration via adeno-sine A2 B receptor activation.This study introduces a controlled-release system for localized adenosine delivery,fostering human mesenchymal stromal cell(hMSC)differentiation into functional bone cells.The study investi-gates how the ratio of lactic acid to glycolic acid in microparticles can influence adenosine release and explores the downstream effects on gene expression and metabolic profiles of osteogenic differentiation in hMSCs cultured in growth and osteoinductive media.Insights into adenosine-modulated signalling pathways during MSC differenti-ation,with osteogenic factors,provide a comprehensive understanding of the pathways involved.Analysing gene expression and metabolic profiles unravels adenosine’s regulatory mechanisms in MSC differentiation.Sustained adenosine release from microparticles induces mineralization,synergizing with osteogenic media supplements,showcasing the potential of adenosine for treating critical bone defects and metabolic disorders.This study high-lights the efficacy of a polymeric microparticle-based delivery system,offering novel strategies for bone repair.Unveiling adenosine’s roles and associated signalling pathways advances our comprehension of molecular mech-anisms steering bone regeneration,propelling innovative biomaterial,combined with metabolites,approaches for clinical use.展开更多
Ectopic mineralization refers to the deposition of mineralized complexes in the extracellular matrix of soft tissues.Calcific aortic valve disease,vascular calcification,gallstones,kidney stones,and abnormal mineraliz...Ectopic mineralization refers to the deposition of mineralized complexes in the extracellular matrix of soft tissues.Calcific aortic valve disease,vascular calcification,gallstones,kidney stones,and abnormal mineralization in arthritis are common examples of ectopic mineralization.They are debilitating diseases and exhibit excess mortality,disability,and morbidity,which impose on patients with limited social or financial resources.Recent recognition that inflammation plays an important role in ectopic mineralization has attracted the attention of scientists from different research fields.In the present review,we summarize the origin of inflammation in ectopic mineralization and different channels whereby inflammation drives the initiation and progression of ectopic mineralization.The current knowledge of inflammatory milieu in pathological mineralization is reviewed,including how immune cells,pro-inflammatory mediators,and osteogenic signaling pathways induce the osteogenic transition of connective tissue cells,providing nucleating sites and assembly of aberrant minerals.Advances in the understanding of the underlying mechanisms involved in inflammatory-mediated ectopic mineralization enable novel strategies to be developed that may lead to the resolution of these enervating conditions.展开更多
基金Financial support was received from Engineering and Physical Sci-ences Research Council(EPSRC)Reference:EP/P001114/Engineering growth factor microenvironments-a new therapeutic paradigm for re-generative medicine.
文摘Non-healing fractures,a global health concern arising from trauma,osteoporosis,and tumours,can lead to severe disabilities.Adenosine,integral to cellular energy metabolism,gains prominence in bone regeneration via adeno-sine A2 B receptor activation.This study introduces a controlled-release system for localized adenosine delivery,fostering human mesenchymal stromal cell(hMSC)differentiation into functional bone cells.The study investi-gates how the ratio of lactic acid to glycolic acid in microparticles can influence adenosine release and explores the downstream effects on gene expression and metabolic profiles of osteogenic differentiation in hMSCs cultured in growth and osteoinductive media.Insights into adenosine-modulated signalling pathways during MSC differenti-ation,with osteogenic factors,provide a comprehensive understanding of the pathways involved.Analysing gene expression and metabolic profiles unravels adenosine’s regulatory mechanisms in MSC differentiation.Sustained adenosine release from microparticles induces mineralization,synergizing with osteogenic media supplements,showcasing the potential of adenosine for treating critical bone defects and metabolic disorders.This study high-lights the efficacy of a polymeric microparticle-based delivery system,offering novel strategies for bone repair.Unveiling adenosine’s roles and associated signalling pathways advances our comprehension of molecular mech-anisms steering bone regeneration,propelling innovative biomaterial,combined with metabolites,approaches for clinical use.
基金grants 81870805 from the National Natural Science Foundation of China,grant 2020TD-033 from the Shaanxi Key Scientific and Technological Innovation Team and by the Youth Innovation Team of Shaanxi Universities.
文摘Ectopic mineralization refers to the deposition of mineralized complexes in the extracellular matrix of soft tissues.Calcific aortic valve disease,vascular calcification,gallstones,kidney stones,and abnormal mineralization in arthritis are common examples of ectopic mineralization.They are debilitating diseases and exhibit excess mortality,disability,and morbidity,which impose on patients with limited social or financial resources.Recent recognition that inflammation plays an important role in ectopic mineralization has attracted the attention of scientists from different research fields.In the present review,we summarize the origin of inflammation in ectopic mineralization and different channels whereby inflammation drives the initiation and progression of ectopic mineralization.The current knowledge of inflammatory milieu in pathological mineralization is reviewed,including how immune cells,pro-inflammatory mediators,and osteogenic signaling pathways induce the osteogenic transition of connective tissue cells,providing nucleating sites and assembly of aberrant minerals.Advances in the understanding of the underlying mechanisms involved in inflammatory-mediated ectopic mineralization enable novel strategies to be developed that may lead to the resolution of these enervating conditions.
