Open AccessDifferential effects of aging on human chondrocyte responses to transforming growth factor β. Increased pyrophosphate production and decreased cell proliferation
Author(s) -
Rosen Fred,
McCabe Greg,
Quach Jacqueline,
Solan Joell,
Terkeltaub Robert,
Seegmiller J. Edwin,
Lotz Martin
Publication year - 1997
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.1780400712
Subject(s) - chondrocyte , transforming growth factor , endocrinology , osteoarthritis , medicine , cartilage , intracellular , cell growth , pyrophosphate , alkaline phosphatase , chemistry , growth factor , cell , biochemistry , anatomy , pathology , receptor , enzyme , alternative medicine
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 β1 (TGFβ1) on PPi levels in the media and cell lysates of chondrocytes were investigated. In addition, the effects of TGFβ on PPi accumulation were compared with chondrocyte proliferation. Results . TGFβ1 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 TGFβ1 led to a similar increase in total intracellular protein in both age groups. Although TGFβ 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 TGFβ‐induced chondrocyte proliferation, whereas these same cells showed an increased response with respect to PPi elaboration. Conclusion . These results show that aging differentially affected TGFβ‐induced PPi accumulation versus proliferation in human articular chondrocytes. These differences in TGFβ response are likely to contribute to the development of age‐associated cartilage diseases such as osteoarthritis.