| First Author | Kim H | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 3 | Pages | 1312-8 |
| PubMed ID | 23293355 | Mgi Jnum | J:193018 |
| Mgi Id | MGI:5467429 | Doi | 10.4049/jimmunol.1202525 |
| Citation | Kim H, et al. (2013) Dynein light chain LC8 inhibits osteoclast differentiation and prevents bone loss in mice. J Immunol 190(3):1312-8 |
| abstractText | NF-kappaB is one of the key transcription factors activated by receptor activator of NF-kappaB ligand (RANKL) during osteoclast differentiation. The 8-kDa dynein L chain (LC8) was previously identified as a novel NF-kappaB regulator. However, its physiological role as an NF-kappaB inhibitor remains elusive. In this study, we showed the inhibitory role of LC8 in RANKL-induced osteoclastogenesis and signaling pathways and its protective role in osteolytic animal models. LC8 suppressed RANKL-induced osteoclast differentiation, actin ring formation, and osteoclastic bone resorption. LC8 inhibited RANKL-induced phosphorylation and subsequent degradation of IkappaBalpha, the expression of c-Fos, and the consequent activation of NFATc1, which is a pivotal determinant of osteoclastogenesis. LC8 also inhibited RANKL-induced activation of JNK and ERK. LC8-transgenic mice exhibited a mild osteopetrotic phenotype. Moreover, LC8 inhibited inflammation-induced bone erosion and protected against ovariectomy-induced bone loss in mice. Thus, our results suggest that LC8 inhibits osteoclast differentiation by regulating NF-kappaB and MAPK pathways and provide the molecular basis of a new strategy for treating osteoporosis and other bone diseases. |
