Efferocytosis in inflammatory bone disorders

Efferocytosis, the clearance of apoptotic cells (ACs) by phagocytes, is crucial for bone homeostasis and immune balance. This tightly regulated process depends on molecular markers such as phosphatidylserine on ACs and MERTK on phagocytes. In the bone microenvironment, multiple cell types participate in efferocytosis, including osteal macrophages, mesenchymal stem cells, osteoblasts, and osteoclasts, directly influencing bone remodeling and immune responses. Impaired efferocytosis disrupts bone turnover, exacerbates inflammation, and contributes to inflammatory bone diseases. Despite its recognized importance, the precise mechanisms regulating efferocytosis in osteoimmunology remain underexplored, including specific signaling pathways, cell-specific interactions, and therapeutic applications. Recent advances highlight the therapeutic potential of targeting efferocytosis using modalities and biomaterial-based strategies. This review systematically examines the role of efferocytosis in osteoimmunology, discusses key challenges in its therapeutic translation, and explores emerging strategies to optimize efferocytosis-based interventions for inflammatory bone disorders.