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

Abstract

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-1beta 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 (NFkappaB) inhibitor suggesting a role for NFkappaB in this chondrocyte catabolic response. Chondrocyte production of the NFkappaB-regulated cytokine interleukin-1beta was 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.