HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M600151-JLR200v1 47/8/1739    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rahman, M. M. Articles by Fernandes, G. Search for Related Content PubMed PubMed Citation Articles by Rahman, M. M. Articles by Fernandes, G. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 47, 1739-1748, August 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Conjugated linoleic acid inhibits osteoclast differentiation of RAW264.7 cells by modulating RANKL signaling

Md Mizanur Rahman¹, Arunabh Bhattacharya¹ and Gabriel Fernandes²

Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900

Published, JLR Papers in Press, May 15, 2006.

¹ M. M. Rahman and A. Bhattacharya contributed equally to this work.

² To whom correspondence should be addressed. e-mail: fernandes{at}uthscsa.edu

Bone destruction is a pathological hallmark of several chronic inflammatory diseases, including rheumatoid arthritis, periodontitis, and osteoporosis. Inflammation-induced bone loss of this sort results from increased numbers of bone-resorbing osteoclasts. Numerous studies have indicated that conjugated linoleic acid (CLA) positively influences calcium and bone metabolism. Gene-deletion studies have shown that receptor activator of nuclear factor-B ligand (RANKL) is one of the critical mediators of osteoclastogenesis. In this report, we examine the ability of CLA to suppress RANKL signaling and osteoclastogenesis in RAW264.7 cells, a murine monocytic cell line. Treatment of these cells with RANKL activated nuclear factor-B (NF-B), and preexposure of the cells to CLA significantly suppressed RANKL-induced NF-B activation, including phosphorylation of I-B, degradation of I-B, and nuclear translocation of p65. RANKL induced osteoclastogenesis in these monocytic cells, and CLA inhibited RANKL-induced tumor necrosis factor- production and osteoclast differentiation, including osteoclast-specific genes such as tartrate-resistant acid phosphatase, cathepsin K, calcitonin receptor, and matrix metalloproteinase-9 expression and osteoclast-specific transcription factors such as c-Fos, nuclear factor of activated T-cells expression, and bone resorption pit formation. CLA also inhibited RANKL-induced activation of mitogen-activated protein kinase p38 but had little effect on c-Jun N-terminal kinase activation. Collectively, these data demonstrate for the first time that CLA inhibits osteoclastogenesis by modulating RANKL signaling. Thus, CLA may have important therapeutic implications for the treatment of bone diseases associated with enhanced bone resorption by excessive osteoclastogenesis.

Supplementary key words lipids • monocytes/macrophages • transcription factors • cytokines • cell differentiation • inflammation • signaling pathways • receptor activator of nuclear factor-B ligand

Abbreviations: CLA, conjugated linoleic acid; CTR, calcitonin receptor; EMSA, electrophoretic mobility shift assay; JNK, c-Jun N-terminal kinase; LA, linoleic acid; MAPK, mitogen-activated protein kinase; MMP, matrix metalloproteinase; MNC, multinucleated cell; NFATc1, nuclear factor of activated T-cells; NF-B, nuclear factor-B; RANKL, receptor activator of nuclear factor-B ligand; TNF, tumor necrosis factor; TRAP, tartrate-resistant acid phosphatase

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. E. Butz, G. Li, S. M. Huebner, and M. E. Cook A mechanistic approach to understanding conjugated linoleic acid's role in inflammation using murine models of rheumatoid arthritis Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R669 - R676. [Abstract] [Full Text] [PDF]