Cafeic Acid Inhibits Nfkb Activation Of Osteoclastogenesis Signaling Pathway

INDONESIAN BIOMEDICAL JOURNAL(2011)

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摘要
BACKGROUND: Caffiec acid (3,4-dihydroxycinnamic acids) is involved in various green plants. Based on our previous report, a major component of sweet potato extracts, possibly caffeic acid, was shown as a promising inhibitor of osteoclastogenesis. However, the effect of caffeic acid in inhibiting osteoclastogenesis needs to be confirmed. The underlying mechanism needs to be disclosed as well.METHODS: Caffeic acid in various concentrations was added to in vitro osteoclastogenesis of receptor activator nuclear factor kB ligand (RANKL)-tumor necrosis factor alpha (TNF alpha)-macrophage colony stimulating factor (M-CSF)-induced bone marrow-derived mono macrophage precursor cells (BMMs) and RANKL-TNF alpha-induced RAW264 cells D-Clone (RAW-D cells). Tartrate resistant acid phosphatase (TRAP) staining was performed and IRAP-pcisitive polynucleated cells (PNCs) were counted. For apoptosis analysis, caffeic acid-treated BMMs, RAW-I) cells and osteoclast-like PNCs were subjected to Sub-G I Apoptosis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. To measure NFkB activity, RAW-I) cells were transfected with pNI1B-TA-Luc and subjected to Dual Luciferase Reporter Assay System.RESULTS: Caffeic acid inhibited osteoclastogenesis of RANKL-TNF alpha-M-CSF-induced BMMs as well as RANKL-TNF alpha\-induced RAW-D cells in adose dependent manner, Caffeic acid did not induce apoptosis in BMMs, RAW-D cells and osteoclast-like PNCs. RANKL-TNF alpha induced NFkB activity in RAW-D was diminished by caffeic acid in a dose dependent manner. Significant NFkB activity inhibition was observed starting from I jag! mLcaffeic acid.CONCLUSIONS: Caffeic acid could be a potent osteoclastogenesis inhibitor through inhibition of NFkB activity. Our present study should be further followed up to disclose caffeic acid's possible overlying signaling pathways in inhibiting osteoclastogenesis.
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关键词
caffeic acid, osteoclastogenesis, NFkB, RANKL, TNF alpha
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