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First published online July 23, 2008
doi: 10.1242/10.1242/jcs.028217

Journal of Cell Science 121, 2555-2564 (2008)
Published by The Company of Biologists 2008
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Research Article

The JNK-dependent CaMK pathway restrains the reversion of committed cells during osteoclast differentiation

Eun-Ju Chang1, Jeongim Ha1, Hao Huang1, Hyung Joon Kim1, Jung Hoon Woo2, Youngkyun Lee1, Zang Hee Lee1, Ju Han Kim2 and Hong-Hee Kim1,*

1 Department of Cell and Developmental Biology, BK21 Program, and DRI, Seoul National University, Seoul 110-749, Korea
2 Seoul National University Biomedical Informatics, Seoul National University College of Medicine, Seoul 110-799, Korea

* Author for correspondence (e-mail: hhbkim{at}snu.ac.kr)

Accepted 12 May 2008

Osteoclastogenesis involves the commitment of macrophage-lineage precursors to tartrate-resistant acid phosphatase-positive (TRAP+) mononuclear pre-osteoclasts (pOCs) and subsequent fusion of pOCs to form multinuclear mature osteoclasts. Despite many studies on osteoclast differentiation, little is known about the signaling mechanisms that specifically mediate the osteoclastic commitment. In this study, we found that inhibition of JNK at the pOC stage provoked reversion of TRAP+ cells to TRAP– cells. The conversion to TRAP– cells occurred with concomitant return to the state with higher expression of macrophage antigens, and greater activity of phagocytosis and dendritic-differentiation potential. JNK inhibition at the pOC stage reduced NFATc1 and CaMK levels, and addition of active NFATc1 partially rescued the effect of JNK inhibition. In addition, the level of NFATc1 was decreased by knockdown of CaMK by RNAi and by catalytic inhibition of CaMK, which both caused the reversion of pOCs to macrophages. These data suggest that JNK activity is specifically required for maintaining the committed status during osteoclastogenesis and that the CaMK-NFATc1 pathway is the key element in that specific role of JNK.

Key words: JNK, Osteoclast, Commitment, CaMK, NFATc1






© The Company of Biologists Ltd 2008