Increased Matrix Metalloproteinase-13 Production With Aging by Human Articular Chondrocytes in Response to Catabolic Stimuli

Chondrocyte anabolic activity has been shown to decline with aging, but catabolic activity has received little attention. In this study, the effect of aging on the chondrocyte catabolic response was determined by stimulating isolated human chondrocytes with fibronectin fragments (FN-f) or interleukin-1b and measuring matrix metalloproteinase-13 (MMP-13) production as a catabolic response. A significant age-related increase in chondrocyte MMP-13 production was noted. FN-f stimulation of MMP-13 expression was blocked using a nuclear factor kappa-B (NFjB) inhibitor suggesting a role for NFjB in this chondrocyte catabolic response. Chondrocyte production of the NFjB-regulated cytokine interleukin-1bwas also found to increase with donor age in unstimulated cells. These results demonstrate a significant age-related increase in chondrocyte catabolic responsiveness which could contribute to the development of osteoarthritis in older adults. THE hallmark of osteoarthritis (OA) is progressive lossof articular cartilage to a much greater extent than that which characterizes the normal ‘‘wear and tear’ ’ of aging. However, although it is known that the single greatest risk factor for the development of OA is age, exactly how cartilage aging processes contribute to the development o