Efferocytosis at the frontline of homeostasis: Shaping the bone microenvironment and therapeutic implications in related diseases.

Bone is a dynamic tissue that constantly undergoes remodeling processes throughout life to maintain its structure and integrity. During this process, physiological bone turnover, which is shaped by apoptosis, occurs in cells in the bone microenvironment. The clearance of these apoptotic cells (ACs) is executed by phagocytes through a process called efferocytosis, which simply means taking to the grave "burial." Efferocytosis is a multistage process involving the recognition, binding, internalization, and digestion of ACs, culminating in the resolution of inflammation. Critically, aberrations in efferocytosis lead to the accumulation of apoptotic corpses, impairing tissue homeostasis and contributing to various pathologies as well as bone-related diseases. Emerging evidence suggests that modulating/activating efferocytosis at any stage represents a promising therapeutic strategy for managing bone-related diseases, especially those associated with aging and inflammation. This review discusses the current understanding of the cellular and molecular mechanisms of efferocytosis, its roles within the bone microenvironment, and potential therapeutic interventions targeting efferocytosis in age-related bone diseases.