| First Author | David JP | Year | 2002 |
| Journal | J Cell Sci | Volume | 115 |
| Issue | Pt 22 | Pages | 4317-25 |
| PubMed ID | 12376563 | Mgi Jnum | J:120169 |
| Mgi Id | MGI:3703973 | Doi | 10.1242/jcs.00082 |
| Citation | David JP, et al. (2002) JNK1 modulates osteoclastogenesis through both c-Jun phosphorylation-dependent and -independent mechanisms. J Cell Sci 115(Pt 22):4317-25 |
| abstractText | Phosphorylation of the N-terminal domain of Jun by the Jun kinases (JNKs) modulates the transcriptional activity of AP-1, a dimeric transcription factor typically composed of c-Jun and c-Fos, the latter being essential for osteoclast differentiation. Using mice lacking JNK1 or JNK2, we demonstrate that JNK1, but not JNK2, is specifically activated by the osteoclast-differentiating factor RANKL. Activation of JNK1, but not JNK2, is required for efficient osteoclastogenesis from bone marrow monocytes (BMMs). JNK1 protects BMMs from RANKL-induced apoptosis during differentiation. In addition, BMMs from mice carrying a mutant of c-Jun phosphorylation sites (JunAA/JunAA), as well as cells lacking either c-Jun or JunD, which is another JNK substrate, revealed that c-Jun phosphorylation and c-Jun itself, but not JunD, are essential for efficient osteoclastogenesis. Moreover, JNK1-dependent c-Jun phosphorylation in response to RANKL is not involved in the anti-apoptotic function of JNK1. Thus, these data provide genetic evidence that JNK1 activation modulates osteoclastogenesis through both c-Jun-phosphorylation-dependent and -independent mechanisms. |
