Aging profoundly impacts bone homeostasis and regeneration,yet the cellular and molecular mechanisms underlying periosteal aging remain poorly understood.Using single-cell RNA sequencing,we profiled the periosteum of ...Aging profoundly impacts bone homeostasis and regeneration,yet the cellular and molecular mechanisms underlying periosteal aging remain poorly understood.Using single-cell RNA sequencing,we profiled the periosteum of 3-,9-,and 18-month-old mice,which revealed age-related shifts in progenitor,neutrophil,and macrophage subpopulations.Aging reduced mesenchymal cell populations and impaired osteogenic potential,may contribute to periosteal homeostasis.Periosteal progenitor subsets exhibited distinct aging trajectories:Dpt^(+)fibrous-layer cells undergoing early senescence,while Postn^(+)progenitors showed osteogenic decline.Aging also shifted immune profiles,increasing inflammatory Cd38^(hi)macrophages and dysfunctional Nlrp3^(hi)neutrophils,further disrupting bone homeostasis.Notably,aged progenitor cells upregulated CSF1 and CXCL signaling,driving macrophage and neutrophil infiltration,exacerbating bone loss.Our findings provide a comprehensive periosteal aging atlas,revealing aging-associated alterations in progenitor-immune crosstalk that may influence bone tissue dynamics,and offering insights into potential targets for age-related skeletal conditions.展开更多
基金supported by the National Natural Science Foundation of China(Youth Program,Grant No.82202699,82402794),the Shanghai Sailing Program for Young Scientific Talents(Grant No.22YF1443300,23YF1441500)the Independent Original Research Program of Tongji University(Grant No.22120220652)+1 种基金Clinical Cultivation and Key Project of Yangzhi Rehabilitation Hospital(Sunshine Rehabilitation Centre)(2024CRZD008)the Postdoctoral Fellowship Program of CPSF(GZC20251556).
文摘Aging profoundly impacts bone homeostasis and regeneration,yet the cellular and molecular mechanisms underlying periosteal aging remain poorly understood.Using single-cell RNA sequencing,we profiled the periosteum of 3-,9-,and 18-month-old mice,which revealed age-related shifts in progenitor,neutrophil,and macrophage subpopulations.Aging reduced mesenchymal cell populations and impaired osteogenic potential,may contribute to periosteal homeostasis.Periosteal progenitor subsets exhibited distinct aging trajectories:Dpt^(+)fibrous-layer cells undergoing early senescence,while Postn^(+)progenitors showed osteogenic decline.Aging also shifted immune profiles,increasing inflammatory Cd38^(hi)macrophages and dysfunctional Nlrp3^(hi)neutrophils,further disrupting bone homeostasis.Notably,aged progenitor cells upregulated CSF1 and CXCL signaling,driving macrophage and neutrophil infiltration,exacerbating bone loss.Our findings provide a comprehensive periosteal aging atlas,revealing aging-associated alterations in progenitor-immune crosstalk that may influence bone tissue dynamics,and offering insights into potential targets for age-related skeletal conditions.
