Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 168, Issue 1, Pages 131-140Publisher
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2006.050369
Keywords
-
Categories
Funding
- NATIONAL INSTITUTE ON AGING [R01AG013857] Funding Source: NIH RePORTER
- NIA NIH HHS [2R01AG13857-05] Funding Source: Medline
Ask authors/readers for more resources
Articular cartilage degeneration in ostcoarthritis (OA) involves type H collagen degradation and chondrocyte differentiation (hypertrophy). Because these changes resemble growth plate remodeling, we hypothesized that collagen degradation may be inhibitable by growth factors known to suppress growth plate hypertrophy, namely transforming growth factor (TGF)-beta 2, fibroblast growth factor (FGF)-2, and insulin. Full-depth explants of human OA knee articular cartilage from arthroplasty were cultured with TGF-beta 2, FGF-2, and insulin in combination (growth factors) or individually. In cultured explants from five OA patients, collagenase-mediated type 11 collagen cleavage was significantly down-regulated by combined growth factors as measured by enzyme-linked inummosorbent assay. individually, FGF-2 and insulin failed to inhibit collagen cleavage in some OA explants whereas TGF-beta 2 reduced collagen cleavage in these 5 explants and in 19 additional explants. Moreover, TGF-beta 2 effectively suppressed cleavage at low concentrations. Together or individually these growth factors did not inhibit glycosaminoglycan (primarily aggrecan) degradation while TGF-beta 2 occasionally did. Semiquantitative reverse transcriptase-polymerase chain reaction of articular cartilage from six OA patients revealed that TGF-beta 2 suppressed expression of matrix metalloproteinase-13 and matrix metalloproteinase-9, early (PTHrP) and late (COL10A1) differentiation-related genes, and proinflammatory cytokines (interleukin-1,6, tumor necrosis factor-alpha). In contrast, TGF-beta 2 up-regulated PGES-1 expression and prostaglandin E-2 release. These observations show that TGF-beta 2 can suppress collagen resorption and chondrocyte differentiation in OA cartilage and that this may be mediated by prostaglandin E-2. Therefore TGF-beta 2 could provide therapeutic control of type II collagen degeneration in OA.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available