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-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.
Forsyth
Christopher B
CB
Department of Internal Medicine, Rush Medical College, Rush University Medical Center, Chicago, Illinois, USA.
Cole
Ada
A
Murphy
Gillian
G
Bienias
Julia L
JL
Im
Hee-Jeong
HJ
Loeser
Richard F
RF
D000368:Aged; D000375:Aging / Q000378:metabolism*; D000843:Ankle Joint; D002358:Cartilage, Articular / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology*; D017364:Collagenases / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D007719:Knee Joint; D053509:Matrix Metalloproteinase 13; D008875:Middle Aged
D005353:Fibronectins; D007375:Interleukin-1; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13