Journals of Gerontology Series A: Biological Sciences and Medical Sciences Large Type Edition
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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 60:1118-1124 (2005)
© 2005 The Gerontological Society of America

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

Christopher B. Forsyth1, Ada Cole2, Gillian Murphy3, Julia L. Bienias1, Hee-Jeong Im1,2 and Richard F. Loeser, Jr1,2,

1 Departments of Internal Medicine
2 Biochemistry, Rush Medical College, Rush University Medical Center, Chicago, Illinois.
3 Cambridge Institute for Medical Research, Department of Oncology, University of Cambridge, United Kingdom.

Address correspondence to Richard F. Loeser, Jr., MD, Chief, Section of Molecular Medicine, The Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157. E-mail: rloeser{at}wfubmc.edu

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-1ß 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 (NF{kappa}B) inhibitor suggesting a role for NF{kappa}B in this chondrocyte catabolic response. Chondrocyte production of the NF{kappa}B-regulated cytokine interleukin-1ß 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.






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