RANK Proteins

RANK (TNFRSF11A), is the receptor activator of nuclear factor-κB (NF-κB), has originally been described to play key roles in bone metabolism and the immune system. RANK belongs to tumor necrosis factor receptor superfamily, acts function during osteoclasts differentiation and activation. RANK expressed by osteoblast/stromal cells, ubiquitous expression with high levels in skeletal muscle, thymus, liver, colon, small intestine and adrenal gland. However, osteoblast typically are present in large numbers in giant cell tumors of bone (GCTBs), suggesting the affect of expressing factors in tumors that stimulate osteoclasts precursor recruitment and differentiation^[1]. RANK binds RANKL, the receptor activator of NF-κB ligand, to trigger RANKL/RANK/osteoprotegerin (OPG) system to regulate bone resorption. Specifically, the RANKL/RANK signaling pathway promotes the formation of multicellular osteoclast precursors and ensures the activation and survival of multicellular osteoclasts under normal bone remodeling and various pathological conditions. OPG protects bone from excessive bone resorption by competitively binding to RANKL and hindering RANK binding to RANKL^[2]. In addition to RANK's contribution to bone metabolism, the RANKL/RANK system is also involved in dendritic cell (DC)-T cell interactions. In rheumatoid synovium and lymph node pairs, the expression levels of RANK and RANKL can be used as markers to determine the interaction between dendritic cells and T cells^[3]. Moreover, RANKL-RANK system is critical in the formation of mammary epithelia in lactating females and the thermoregulation of the central nervous system. As them under the tight control of the female sex hormones estradiol and progesterone, RANKL-RANK causes osteoporosis in postmenopausal women when circulating female sex hormones decrease. Furthermore, RANKL-RANK signaling also plays a critical role in other bone pathologies, bone metastasis or hormone-driven breast cancer^[4]. The homology of RANK protein in human and mouse was low, and the sequence similarity is 69.32%.

References: