Editorial: Regulation of osteoclast differentiation in autoimmune and inflammatory diseases

Bone remodeling is a dynamic and tightly regulated process that relies on a fine balance between deposition and resorption of the unique mineralized extracellular matrix (ECM) of the musculoskeletal system. Bone-resorbing osteoclasts are multinucleated cells that originate primarily from bone-marrow myeloid and, in specific conditions, extramedullary erythromyeloid progenitors through the combined action of Macrophage Colony-Stimulating Factor (M-CSF) and Receptor Activator of Nuclear Factor k B-Ligand (RANK-L). In addition to these canonical osteoclastogenic stimuli, differentiation, activation, and recycling of osteoclasts are sustained by other soluble, ECM, and cell-borne factors, including bone and immune cell-derived inflammatory mediators (e.g., TNF-a, IL-1b, IL-6, IL-17, IL-23). When in excess over their physiological concentration, these might trigger and maintain a chronic status of local and/or systemic inflammation that eventually leads to hyperosteoclastogenesis and osteolysis, both of which are common traits of autoimmune (e.g., rheumatoid arthritis, inflammatory bowel disease) and inflammatory/infectious (e.g., osteomyelitis and periodontitis) diseases of the bone. Despite impressive progress in osteoimmunology, the cellular and molecular mechanisms underpinning the disregulation of osteoclastogenesis in bone pathology are largely unknown