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

Md Mizanur Rahman, Arunabh Bhattacharya, Gabriel Fernandes

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

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-κB 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-κB (NF-κB), and preexposure of the cells to CLA significantly suppressed RANKL-induced NF-κB activation, including phosphorylation of I-κBα, degradation of I-κBα, and nuclear translocation of p65. RANKL induced osteoclastogenesis in these monocytic cells, and CLA inhibited RANKL-induced tumor necrosis factor-α production and osteoclast differentiation, including osteoclast-specific genes such as tartrate-resistant acid phosphatase, cathepsin K, calcitonin receptor, andmatrix 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.

Original languageEnglish (US)
Pages (from-to)1739-1748
Number of pages10
JournalJournal of lipid research
Volume47
Issue number8
DOIs
StatePublished - Aug 18 2006

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Keywords

  • Cell differentiation
  • Cytokines
  • Inflammation
  • Lipids
  • Monocytes/macrophages
  • Receptor activator of nuclear factor-κB ligand
  • Signaling pathways
  • Transcription factors

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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