RANKL

Full name: Receptor activator of nuclear factor-kappa B ligand

Aliases:1 TNFSF-11, TRANCE, OPGL, and ODF

Size:2 ~35 kDa

Family:2 TNF cytokine superfamily

Receptors:2 RANK and OPG

Major cellular sources:1,3,4 Osteoblasts, osteocytes, T cells, bone marrow stromal cells, and immune cells

Major cellular targets:5,6 Osteoclast precursor and mature osteoclast cells

Disease states associated with:1,3 Bone metabolism, rheumatoid arthritis, osteoporosis, osteopetrosis, and inflammatory bowel disease

Major physiologic functions:

  • Osteoblasts, osteocytes, and T cells produce RANKL, and its expression is induced by certain osteoclastogenic factors such as vitamin D3, prostaglandin E2, parathyroid hormone, IL-1, IL-6, IL-11, IL-17, and TNF-α.1,4 Subsequently, RANKL binds to and activates its receptor RANK on immature and mature osteoclasts, which promotes osteoclast formation, function, and survival.6

  • OPG, a member of the TNFR superfamily, is a soluble decoy receptor and functions as a RANK inhibitor by preventing RANK activation by binding to RANKL with a higher affinity, consequently inhibiting bone resorption.1,2,3,6

IL: interleukin; ODF: osteoclast differentiation factor; OPG: osteoprotegerin; OPGL: OPG ligand; RANK: receptor activator of nuclear factor-kappa B; TNF: tumor necrosis factor; TNFR: TNF receptor; TNFSF: TNF ligand superfamily member; TRANCE: TNF-related activation-induced cytokine.

References:

  • 1.

    Okamoto K, Nakashima T, Shinohara M, et al. Physiol Rev. 2017;97:1295-1349.

  • 2.

    Nelson CA, Warren JT, Wang MW, Teitelbaum SL, Fremont DH. Structure. 2012;20:1971-1982.

  • 3.

    Ono T, Hayashi M, Sasaki F, Nakashima T. Inflamm Regen. 2020;40:2.

  • 4.

    Nakashima T, Hayashi M, Fukunaga T, et al. Nat Med. 2011;17:1231-1234.

  • 5.

    Fuller K, Wong B, Fox S, Choi Y, Chambers TJ. J Exp Med. 1998;188:997-1001.

  • 6.

    Dempster DW, Lambing CL, Kostenuik PJ, Grauer A. Clin Ther. 2012;34:521-536.