Unraveling the intricacies of osteoclast differentiation and maturation: insight into novel therapeutic strategies for bone-destructive diseases

Osteoclasts are the principal cells that efficiently resorb bone. Numerous studies have attempted to reveal the molecular pathways leading to the differentiation and activation of osteoclasts to improve the treatment and prevention of osteoporosis and other bone-destructive diseases. While the cumulative knowledge of osteoclast regulatory molecules, such as receptor activator of nuclear factor-kB ligand (RANKL) and nuclear factor of activated T cells 1 (NFATc1), contributes to the understanding of the developmental progression of osteoclasts, little is known about how the discrete steps of osteoclastogenesis modify osteoclast status but not the absolute number of osteoclasts. The regulatory mechanisms involved in osteoclast maturation but not those involved in differentiation deserve special attention due to their potential use in establishing a more effective treatment strategy: targeting late-phase differentiation while preserving coupled bone formation. Recent studies have shed light on the molecules that govern late-phase osteoclast differentiation and maturation, as well as the metabolic changes needed to adapt to shifting metabolic demands. This review outlines the current understanding of the regulation of osteoclast differentiation, as well as osteoclast metabolic adaptation as a differentiation control mechanism. Additionally, this review introduces molecules that regulate the late-phase osteoclast differentiation and thus minimally impact coupled bone formation. This study explores the process of bone remodeling, particularly the role of osteoclasts (cells that break down bone) and osteoblasts (cells that build new bone). There is a lack of understanding about the biology of the osteoclast differentiation process (the process by which a cell changes from one type to another), which is vital for maintaining bone health. The scientists reviewed how osteoclast differentiation is regulated, focusing on cell signaling (communication between cells) and metabolic adaptation (how cells change their metabolism to survive). They discovered certain molecules could change osteoclast-mediated bone breakdown without affecting bone formation, potentially serving as treatment targets for diseases that destroy bone. The study concludes that understanding the molecular complexities of late-phase osteoclast differentiation will help improve the treatment and prevention of osteoporosis and other bone-destructive diseases.This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.