Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand.


Journal Article

A receptor that mediates osteoprotegerin ligand (OPGL)-induced osteoclast differentiation and activation has been identified via genomic analysis of a primary osteoclast precursor cell cDNA library and is identical to the tumor necrosis factor receptor (TNFR) family member RANK. The RANK mRNA was highly expressed by isolated bone marrow-derived osteoclast progenitors and by mature osteoclasts in vivo. Recombinant OPGL binds specifically to RANK expressed by transfected cell lines and purified osteoclast progenitors. Transgenic mice expressing a soluble RANK-Fc fusion protein have severe osteopetrosis because of a reduction in osteoclasts, similar to OPG transgenic mice. Recombinant RANK-Fc binds with high affinity to OPGL in vitro and blocks osteoclast differentiation and activation in vitro and in vivo. Furthermore, polyclonal Ab against the RANK extracellular domain promotes osteoclastogenesis in bone marrow cultures suggesting that RANK activation mediates the effects of OPGL on the osteoclast pathway. These data indicate that OPGL-induced osteoclastogenesis is directly mediated through RANK on osteoclast precursor cells.

Full Text

Cited Authors

  • Hsu, H; Lacey, DL; Dunstan, CR; Solovyev, I; Colombero, A; Timms, E; Tan, HL; Elliott, G; Kelley, MJ; Sarosi, I; Wang, L; Xia, XZ; Elliott, R; Chiu, L; Black, T; Scully, S; Capparelli, C; Morony, S; Shimamoto, G; Bass, MB; Boyle, WJ

Published Date

  • March 1999

Published In

Volume / Issue

  • 96 / 7

Start / End Page

  • 3540 - 3545

PubMed ID

  • 10097072

Pubmed Central ID

  • 10097072

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.96.7.3540


  • eng