Dynein light chain LC8 inhibits osteoclast differentiation and prevents bone loss in mice

Hyeryeon Kim, Seungha Hyeon, Hojin Kim, Yoohee Yang, Ji Young Huh, Doo Ri Park, Hyojung Lee, Dong Hyun Seo, Han Sung Kim, Soo Young Lee, Woojin Jeong

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

NF-kB is one of the key transcription factors activated by receptor activator of NF-kB ligand (RANKL) during osteoclast differentiation. The 8-kDa dynein L chain (LC8) was previously identified as a novel NF-kB regulator. However, its physiological role as an NF-kB 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 IkBa, 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-kB and MAPK pathways and provide the molecular basis of a new strategy for treating osteoporosis and other bone diseases.

Original languageEnglish
Pages (from-to)1312-1318
Number of pages7
JournalJournal of Immunology
Volume190
Issue number3
DOIs
StatePublished - 1 Feb 2013

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