组织工程与重建外科杂志2026，Vol.22Issue(1)：62-72,11.DOI:10.3969/j.issn.1673-0364.2026.01.008
单细胞测序解析T细胞-破骨细胞基因互作调控大段骨缺损有序再生
T cell-osteoclast interactions regulating the orderly regeneration of critical-sized bone defects by single-cell sequencing
摘要
Abstract
Objective To investigate the dynamic changes of the immune microenvironment during critical-sized bone defect repair and elucidate the regulatory role of T cells in bone regeneration.Methods A critical-sized bone defect model was established in pigs and mice.Regenerating tissues from steady state and multiple postoperative time points were collected for single-cell RNA sequencing(scRNA-seq).After data preprocessing,dimension reduction,clustering,and cell-type annotation,T cells and myeloid populations were further extracted for subcluster identification,differential gene expression analysis,pathway enrichment,and intercellular communication analysis.Functional validation was performed in T cell-deficient mice,and bone regeneration outcomes were assessed using Micro-CT.Results scRNA-seq analysis identified 10 major cell types,with T cells and myeloid cells rapidly recruited during the early regenerative phase and exhibiting time-dependent functional reprogramming.T cells were classified into 7 subclusters,among which CD8⁺ T cell subclusters expanded markedly during bone repair and showed elevated expression of the chemokine CCL5.Myeloid cells were subdivided into 5 subpopulations,and osteoclasts were prominently increased and activated during the bone reconstruction phase.Intercellular interaction analysis indicated that CD8⁺ T cells promoted osteoclast migration and functional activation through the CCL5-CCR5 signaling axis.In T cell-deficient mice,excessive bone formation and ectopic ossification were observed,accompanied by a reduced osteoclast population and hyperactivation of osteogenic pathways.Conclusion During critical-sized bone defect repair,T cells and myeloid cells undergo temporally coordinated recruitment and functional transitions.CD8⁺ T cells regulate osteoclast recruitment and activation via the CCL5-CCR5 signaling axis,maintaining the balance between bone formation and resorption,thereby ensuring orderly bone regeneration and structural reconstruction.关键词
大段骨缺损/骨免疫学/骨再生/单细胞测序/T细胞/破骨细胞Key words
Critical-sized bone defect/Osteoimmunology/Bone regeneration/Single-cell sequencing/T cells/Osteoclasts分类
医药卫生引用本文复制引用
吴其峰,闫杨轩宇,冯馨仪,余宝富,乔云波,魏皎..单细胞测序解析T细胞-破骨细胞基因互作调控大段骨缺损有序再生[J].组织工程与重建外科杂志,2026,22(1):62-72,11.基金项目
国家自然科学基金(82371668,82302820,82372546). （82371668,82302820,82372546）
