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

Title
Dynein light chain LC8 inhibits osteoclast differentiation and prevents bone loss in mice
Authors
Kim H.Hyeon S.Yang Y.Huh J.Y.Park D.R.Lee H.Seo D.-H.Kim H.-S.Lee S.Y.Jeong W.
Ewha Authors
이수영정우진
SCOPUS Author ID
이수영scopus; 정우진scopus
Issue Date
2013
Journal Title
Journal of Immunology
ISSN
0022-1767JCR Link
Citation
vol. 190, no. 3, pp. 1312 - 1318
Indexed
SCI; SCIE; SCOPUS WOS scopus
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. Copyright © 2013 by The American Association of Immunologists, Inc.
DOI
10.4049/jimmunol.1202525
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자연과학대학 > 생명과학전공 > Journal papers
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