Accumulation of advanced glycation end products decreases collagen turnover by bovine chondrocytes.
The integrity of the collagen network is essential for articular cartilage to fulfill its function in load support and distribution. Damage to the collagen network is one of the first characteristics of osteoarthritis. Since extensive collagen damage is considered irreversible, it is crucial that chondrocytes maintain a functional collagen network. We investigated the effects of advanced glycation end products (AGEs) on the turnover of collagen by articular cartilage chondrocytes. Increased AGE levels (by culturing in the presence of ribose) resulted in decreased collagen synthesis (P < 0.05) and decreased MMP-mediated collagen degradation (P < 0.02). The latter could be attributed to increased resistance of the collagen network to MMPs (P < 0.05) as well as the decreased production of MMPs by chondrocytes (P < 0.02). Turnover of a protein is determined by its synthesis and degradation rates and therefore these data indicate that collagen turnover is decreased at enhanced AGE levels. Since AGE levels in human cartilage increase approximately 50 fold between age 20 and 80, cartilage collagen turnover likely decreases with increasing age. Impaired collagen turnover adversely affects the capacity of chondrocytes to remodel and/or repair its extracellular matrix. Consequently, age-related accumulation of AGE (via decreased collagen turnover) may contribute to the development of cartilage damage in osteoarthritis.
DeGroot
J
J
Gaubius Laboratory, TNO Prevention and Health, Leiden, 2301 CE, The Netherlands. J.DeGroot@pg.tno.nl
Verzijl
N
N
Budde
M
M
Bijlsma
J W
JW
Lafeber
F P
FP
TeKoppele
J M
JM
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010003:Osteoarthritis / Q000209:etiology; D012266:Ribose / Q000494:pharmacology
D004792:Enzyme Precursors; D017127:Glycation End Products, Advanced; D012266:Ribose; D003094:Collagen; D020782:Matrix Metalloproteinases