Unraveling the Multifaceted Roles of Tissue-Resident Macrophages: Focus on Bone Homeostasis and Regeneration

Tissue-resident macrophages (TRMs) are essential regulators of tissue homeostasis and regeneration across multiple organs. While their roles in systems such as the liver, brain, and skin have been increasingly clarified, their functions in bone remain markedly understudied. This review begins by outlining the established roles of TRMs in immune regulation and tissue repair to provide a conceptual framework for understanding their skeletal counterparts, known as osteal resident macrophages (ORMs). We then summarize current evidence for ORM involvement in bone homeostasis and regeneration and highlight the major challenges in bone TRM research. Clarifying the cellular identity and regulation of ORMs will help define their roles in bone homeostasis and repair, and inform future strategies for modulating macrophage function in skeletal disease. Tissue-resident macrophages (TRMs) are essential regulators of tissue homeostasis and regeneration across multiple organs. While their roles in systems such as the liver, brain, and skin have been increasingly clarified, their functions in bone remain markedly understudied. This review begins by outlining the established roles of TRMs in immune regulation and tissue repair to provide a conceptual framework for understanding their skeletal counterparts, known as osteal resident macrophages (ORMs). We then summarize current evidence for ORM involvement in bone homeostasis and regeneration and highlight the major challenges in bone TRM research. Clarifying the cellular identity and regulation of ORMs will help define their roles in bone homeostasis and repair, and inform future strategies for modulating macrophage function in skeletal disease.