Friday, December 4, 2009


Biological effects of the plant-derived polyphenol resveratrol in human articular cartilage and chondrosarcoma cells.

"RSV is chondroprotective for articular cartilage in rabbit models for arthritis{Can this translate to height benefits?}. Effects of RSV on human articular cartilage homeostasis were studied by assessing production of matrix-degrading enzymes (MMP-13, ADAMTS4, and ADAMTS5), as well as proteoglycan production and synthesis. The counteractions of RSV against catabolic factors (e.g., FGF-2 or IL-1β) were examined by in vitro and ex vivo using monolayer, three-dimensional alginate beads and cartilage explants cultures, respectively. RSV improves cell viability of articular chondrocytes and effectively antagonizes cartilage-degrading protease production that was initiated by catabolic and/or anti-anabolic cytokines in human articular chondrocytes. RSV significantly enhances BMP7-promoted proteoglycan synthesis. RSV inhibits the activation of transcription factors involved in inflammation and cartilage catabolic signaling pathways, including direct downstream regulators of MAPK (e.g., AP-1, PEA3) and NFκB. RSV selectively compromises survival of human chondrosarcoma cells, but not primary articular chondrocytes, revealing cell-specific activity of RSV on non-tumorigenic versus tumor-derived cells. RSV exerts its chondroprotective functions, in part, by deactivating p53-induced apoptosis in human primary chondrocytes, but not human chondrosarcoma."

"signaling cascades generated by inflammatory cytokines (e.g., IL-1) or fibroblast growth factor-2 (FGF-2 or basic FGF) favor catabolism by stimulating protease production and inhibiting proteoglycan deposition in human adult articular cartilage or intervertebral disc tissue via ERK/MAPK activation"

"FGF-2 mediates striking antagonistic effects on cartilage anabolic activity in conjunction with IGF-1 and BMP7, and both FGF-2 and IL-1 modify chondrocyte gene expression when stimulated by mechanical injury "

"p53 DNA binding activity is significantly stimulated by IL-1β (10 ng/ml) along with AP-1, AP-2, Ets1/PEA3, NFκB, p53, Sp1, and multiple STATs that are critical for cytokine signals"

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