Fig. 1
From: RANKL biology: bone metabolism, the immune system, and beyond
RANKL in bone metabolism. a The RANKL–RANK interaction in bone development and remodeling. Hypertrophic chondrocytes and osteoblasts function as the source of RANKL during growth. After the growth period, osteocytes are the major source of RANKL. RANKL induces the differentiation of osteoclasts, which resorb bone matrix. b RANKL–RANK interaction in bone and joint diseases related to immobility and aging. The bone loss induced by unloading is induced by osteocyte RANKL. B cell RANKL is reported to partially contribute to the bone loss in postmenopausal osteoporosis, as well. c In the lesion that occur in rheumatoid arthritis, synovial fibroblasts stimulated with pro-inflammatory cytokines, including IL-17, express RANKL and enhance osteoclastogenesis. In periodontitis, RANKL is mainly provided by PDL cells and osteoblasts. (see also Table 2). The IL-17 in these processes is produced by TH17 cells stimulated by IL-6. TH17 cells (exFoxp3 TH17 cells, in particular) express RANKL as well. RANKL receptor activator of NF-κB ligand, RANK receptor activator of NF-κB, TH17 cell T helper 17 cell, PDL periodontal ligament