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Reduced SIRT1 activity and levels during osteoarthritis (OA), promotes gradual loss of cartilage. Loss of cartilage matrix is accompanied by an increase of matrix metalloproteinase 13 (MMP13), partially due to enhanced LEF1 transcriptional activity. Here we assess the role of SIRT1 in LEF1-mediated MMP13 gene expression in human osteoarthritic chondrocytes. Results show that MMP13 protein levels and enzymatic activity decreased significantly during SIRT1 overexpression or activation by resveratrol. Conversely, MMP13 gene expression was reduced in chondrocytes transfected with SIRT1 siRNA or treated with nicotinamide (NAM), a sirtuin inhibitor. Chondrocytes challenged with IL-1β, a cytokine involved in OA pathogenesis, enhanced LEF1 protein levels and gene expression, resulting in increased MMP13 gene expression, however, overexpression of SIRT1 during IL-1β challenge impeded LEF1 levels and MMP13 gene expression. While previous reports showed that LEF1 binds to the MMP13 promoter and transactivates its expression, we observed that SIRT1 repressed LEF1 protein and mRNA expression, ultimately reducing LEF1 transcriptional activity, as judged by luciferase assay. Finally, mice articular cartilage from Sirt1 nulls presented increased LEF1 and MMP13 protein levels, similar to human OA cartilage. Thus, demonstrating for the first time that SIRT1 represses MMP13 in human OA chondrocytes, which appears to be mediated, at least in part, through repression of the transcription factor LEF1, a known modulator of MMP13 gene expression.
Next came a one-sided bout against heavy underdog Gary "Big Daddy" Goodridge at Pride Total Elimination 2003 .  Emelianenko took down Goodridge after wobbling him with standing combinations, then finished him with ground and pound in the first round by referee stoppage. Emelianenko broke his hand in this fight, resulting in surgery.  He has since reinjured this hand, leading to several postponed bouts.  In 2011, Goodridge recalled his fight with Emelianenko; "Fedor hits so hard, I don't remember anything (from the fight). No one has his speed and power combo. He fought for 10 years at the top. He doesn't owe anything else to the sport."