KLF15 Regulates the Expression of MMP-3 in Human Chondrocytes.

Abstract

Imbalance of metabolism on catabolic and anabolic molecules in chondrocytes has been associated with the cartilage damage in osteoarthritis (OA). Matrix metalloproteinase-3 (MMP-3), one of the most important catabolic factors, acts as a cartilage-degrading enzyme, which is associated with the degradation of type II collagen and aggrecan. Kruppel-like factor 15 (KLF15), an important member of the KLFs family, possesses a variety of biological functions. However, the physiological roles of KLF15 in chondrocytes and the pathological progression of OA remain unknown. In the current study, we report that KLF15 is expressed in primary chondrocytes as well as ATDC5 and SW1353 chondrogenic cell lines. Interestingly, KLF15 expression was significantly lower in chondrocytes from OA patients compared with those from normal subjects. Also, we found that tumor necrosis factor α (TNF-α) treatment reduced the expression of KLF15 mediated by p53 in human chondrocytes. Notably, it was shown that KLF15 reduced TNF-α-induced expression of MMP-3 at the transcriptional level. Mechanistically, the chromatin immunoprecipitation assay displayed that KLF15 could bind to the promoter region of MMP-3. Our results suggest that KLF15 might be a novel therapeutic target of OA.