Differential effects of aging on human chondrocyte responses to transforming growth factor beta: increased pyrophosphate production and decreased cell proliferation.
OBJECTIVE
To address the influence of age on inorganic pyrophosphate (PPi) accumulation in human articular chondrocytes.


METHODS
Articular cartilage was obtained from men and women in 2 different age groups: ages 15-55 and 56-91. The effects of transforming growth factor beta1 (TGFbeta1) on PPi levels in the media and cell lysates of chondrocytes were investigated. In addition, the effects of TGFbeta on PPi accumulation were compared with chondrocyte proliferation.


RESULTS
TGFbeta1 increased PPi levels to a greater extent in chondrocytes from subjects in the older age group compared with those obtained from younger subjects. Treatment of chondrocytes with TGFbeta1 led to a similar increase in total intracellular protein in both age groups. Although TGFbeta increased nucleoside triphosphate pyrophosphohydrolase activity and decreased alkaline phosphatase activity, these effects did not differ between the 2 age groups. Analysis of the same cell preparations showed an age-related decrease in TGFbeta-induced chondrocyte proliferation, whereas these same cells showed an increased response with respect to PPi elaboration.


CONCLUSIONS
These results show that aging differentially affected TGFbeta-induced PPi accumulation versus proliferation in human articular chondrocytes. These differences in TGFbeta response are likely to contribute to the development of age-associated cartilage diseases such as osteoarthritis.
Rosen
F
F
Sam and Rose Stein Institute for Research on Aging and University of California-San Diego, La Jolla 92093-0663, USA.
McCabe
G
G
Quach
J
J
Solan
J
J
Terkeltaub
R
R
Seegmiller
J E
JE
Lotz
M
M
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology*; D000469:Alkaline Phosphatase / Q000032:analysis; D002356:Cartilage / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D002455:Cell Division / Q000187:drug effects; D011756:Diphosphates / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014176:Protein Biosynthesis; D011755:Pyrophosphatases / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D011756:Diphosphates; D016212:Transforming Growth Factor beta; D000469:Alkaline Phosphatase; D011755:Pyrophosphatases; C021895:nucleoside triphosphate pyrophosphatase