M2 Macrophages Guide Periosteal Stromal Cell Recruitment and Initiate Bone Injury Regeneration

M2巨噬细胞引导骨膜基质细胞募集并启动骨损伤再生。

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作者:Dazhuang Lu ,Yingfei Zhang ,Shimin Liang ,Yang Li ,Jia Qing ,Lanxin Gu ,Xiuyun Xu ,Zeying Wang ,Xin Gao ,Hao Liu ,Xiao Zhang ,Yongsheng Zhou ,Ping Zhang

Abstract

The periosteum plays a critical role in bone repair and is significantly influenced by the surrounding immune microenvironment. In this study, we employed 10× single-cell RNA sequencing to create a detailed cellular atlas of the swine cranial periosteum, highlighting the cellular dynamics and interactions essential for cranial bone injury repair. We noted that such injuries lead to an increase in M2 macrophages, which are key in modulating the periosteum's immune response and driving the bone regeneration process. These macrophages actively recruit periosteal stromal cells (PSCs) by secreting Neuregulin 1 (NRG1), a crucial factor in initiating bone regeneration. This recruitment process emphasizes the critical role of PSCs in effective bone repair, positioning them as primary targets for therapeutic interventions. Our results indicate that enhancing the interaction between M2 macrophages and PSCs could significantly improve the outcomes of treatments aimed at cranial bone repair and regeneration.

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