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| Content Provider | PubMed Central |
|---|---|
| Author | Hsu, Hailing Lacey, David L. Dunstan, Colin R. Solovyev, Irina Anne, Colombero Timms, Emma Tan, Hong-lin Elliott, Gary Kelley, Michael J. Sarosi, Ildiko Wang, Ling Xia, Xing-zhong Elliott, Robin Chiu, Laura Black, Tabitha Scully, Sheila Capparelli, Casey Morony, Sean Shimamoto, Grant Bass, Michael B. Boyle, William J. |
| Copyright Year | 1999 |
| Abstract | 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. |
| Starting Page | 3540 |
| File Format | |
| ISSN | 10916490 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 7 |
| Volume Number | 96 |
| Language | English |
| Publisher | The National Academy of Sciences |
| Publisher Date | 1999-03-30 |
| Access Restriction | Open |
| Rights Holder | The National Academy of Sciences |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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