Fine‐tuning osteoclastogenesis: An insight into the cellular and molecular regulation of osteoclastogenesis

Abstract

Osteoclasts, the bone-resorbing cells, are essential for the bone remodeling process and are involved in the pathophysiology of several bone-related diseases. The extensive corpus of in vitro research and crucial mouse model studies in the 1990s demonstrated the key roles of monocyte/macrophage colony-stimulating factor, receptor activator of nuclear factor kappa B ligand (RANKL) and integrin αvβ3 in osteoclast biology. Our knowledge of the molecular mechanisms by which these variables control osteoclast differentiation and function has significantly advanced in the first decade of this century. Recent developments have revealed a number of novel insights into the fundamental mechanisms governing the differentiation and functional activity of osteoclasts; however, these mechanisms have not yet been adequately documented. Thus, in the present review, we discuss various regulatory factors including local and hormonal factors, innate as well as adaptive immune cells,noncoding RNAs (ncRNAs), etc., in the molecular regulation of the intricate and tightly regulated process of osteoclastogenesis. ncRNAs have a critical role as epigenetic controllers of osteoclast physiologic activities, including differentiation and bone resorption. The primary ncRNAs, which include micro-RNAs, circular RNAs, and long noncoding RNAs, form a complex network that affects gene transcription activities associated with osteoclast biological activity. Greater knowledge of the involvement of ncRNAs in osteoclast biological activities will contribute to the treatment and management of several skeletal diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis, etc. Moreover, we further outline potential therapies targeting these regulatory pathways of osteoclastogenesis in distinct bone pathologies.

Genetic Deficiency of the Long Pentraxin 3 Affects Osteogenesis and Osteoclastogenesis in Homeostatic and Inflammatory Conditions

“…Bone remodeling is a highly coordinated process that hinges upon the cooperative action of specialized cells of mesenchymal and hematopoietic origin (i.e., osteoblasts and osteoclasts, respectively) and additional contributions from immune cells [26][27][28][29][30]. This process is mediated by the essential players RANKL, OPG, M-CSF, and their cognate receptors and finely regulated by several additional factors including hormones, extracellular matrix components, and inflammatory molecules [31][32][33][34][35][36].…”

Current Perspectives of Protein in Bone Tissue Engineering: Bone Structure, Ideal Scaffolds, Fabrication Techniques, Applications, Scopes, and Future Advances

“…Osteoclasts function by orchestrating these procedures and maintaining the equilibrium in bone remodeling. The process begins when osteoprotegerin (OPG) attaches to RANK, triggering a series of signaling events and gene activation that ultimately leads to the production of osteoclasts . OPG is a cytokine released by osteoblasts that competes with other molecules to block osteoclast production and prevent bone resorption.…”

“…The process begins when osteoprotegerin (OPG) attaches to RANK, triggering a series of signaling events and gene activation that ultimately leads to the production of osteoclasts. 91 OPG is a cytokine released by osteoblasts that competes with other molecules to block osteoclast production and prevent bone resorption. Remodeling is the primary and dynamic process in adult humans for repairing old damaged bones caused by daily physical stress and the effects of aging and preventing their consequences.…”