Accumulation of advanced glycation endproducts reduces chondrocyte-mediated extracellular matrix turnover in human articular cartilage.
OBJECTIVE
The prevalence of osteoarthritis (OAs) increases with age and coincides with the accumulation of advanced glycation endproducts (AGEs) in articular cartilage, suggesting that accumulation of glycation products may be involved in the development of OA. This study was designed to examine the effects of accumulation of AGEs on the turnover of the extracellular matrix of human articular cartilage.


METHODS
Chondrocyte mediated cartilage degradation (GAG release, colorimetric) was measured in human articular cartilage of donors aged 19-82 years (N=30, 4-day culture). In addition, to mimic the age-related increase in AGE levels in vitro, cartilage was cultured in the absence or presence of glucose, ribose or threose. Cartilage degradation and proteoglycan synthesis ((35)SO(2)(-4) incorporation) were measured and related to the degree of cartilage AGE levels (fluorescence at 360/460 nm).


RESULTS
Chondrocyte-mediated degradation of articular cartilage (i.e. GAG release) decreased with increasing age of the cartilage donor (r=-0.43, P< 0.02). In vitro incubation of cartilage with glucose, ribose or threose resulted in a range of AGE levels that was highly correlated to the chondrocyte-mediated cartilage degradation (r=-0.77, P< 0.001, N=26). In addition, in these in vitro glycated cartilage samples, a decrease in proteoglycan synthesis was observed at increasing AGE levels (r=-0.54, P< 0.005, N=25).


CONCLUSIONS
This study shows that an increase in AGE levels negatively affects the proteoglycan synthesis and degradation of articular cartilage. In combination, these two effects reduce the turnover of the cartilage and thereby the maintenance and repair capacity of the tissue. By this mechanism, the age-related increase in cartilage AGE levels may contribute to the development of OA.
DeGroot
J
J
Gaubius Laboratory, TNO Prevention and Health, 2301 CE Leiden, The Netherlands. J.DeGroot@pg.tno.nl
Verzijl
N
N
Jacobs
K M
KM
Budde
M
M
Bank
R A
RA
Bijlsma
J W
JW
TeKoppele
J M
JM
Lafeber
F P
FP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D000704:Analysis of Variance; D002358:Cartilage, Articular / Q000166:cytology* / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D003124:Colorimetry; D005109:Extracellular Matrix / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D011509:Proteoglycans / Q000378:metabolism; D018709:Statistics, Nonparametric
D017127:Glycation End Products, Advanced; D006025:Glycosaminoglycans; D011509:Proteoglycans