| First Author | Feng X | Year | 2001 |
| Journal | J Clin Invest | Volume | 107 |
| Issue | 9 | Pages | 1137-44 |
| PubMed ID | 11342577 | Mgi Jnum | J:120522 |
| Mgi Id | MGI:3706725 | Doi | 10.1172/JCI12040 |
| Citation | Feng X, et al. (2001) A Glanzmann's mutation in beta 3 integrin specifically impairs osteoclast function. J Clin Invest 107(9):1137-44 |
| abstractText | Osteoclastic bone resorption requires cell-matrix contact, an event mediated by the alpha v beta 3 integrin. The structural components of the integrin that mediate osteoclast function are, however, not in hand. To address this issue, we generated mice lacking the beta 3 integrin gene, which have dysfunctional osteoclasts. Here, we show the full rescue of beta 3(-/-) osteoclast function following expression of a full-length beta 3 integrin. In contrast, truncated beta 3, lacking a cytoplasmic domain (h beta 3c), is completely ineffective in restoring function to beta 3(-/-) osteoclasts. To identify the components of the beta 3 cytoplasmic domain regulating osteoclast function, we generated six point mutants known, in other circumstances, to mediate beta integrin signaling. Of the six, only the S(752)P substitution, which also characterizes a form of the human bleeding disorder Glanzmann's thrombasthenia, fails to rescue beta 3(-/-) osteoclasts or restore ligand-activated signaling in the form of c-src activation. Interestingly, the double mutation Y(747)F/Y(759)F, which disrupts platelet function, does not affect the osteoclast. Thus similarities and distinctions exist in the mechanisms by which the beta 3 integrin regulates platelets and osteoclasts. |
