Document Detail

Transforming growth factor-beta2 suppresses collagen cleavage in cultured human osteoarthritic cartilage, reduces expression of genes associated with chondrocyte hypertrophy and degradation, and increases prostaglandin E(2) production.
MedLine Citation:
PMID:  16400016     Owner:  NLM     Status:  MEDLINE    
Articular cartilage degeneration in osteoarthritis (OA) involves type II 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)-beta2, fibroblast growth factor (FGF)-2, and insulin. Full-depth explants of human OA knee articular cartilage from arthroplasty were cultured with TGF-beta2, FGF-2, and insulin in combination (growth factors) or individually. In cultured explants from five OA patients, collagenase-mediated type II collagen cleavage was significantly down-regulated by combined growth factors as measured by enzyme-linked immunosorbent assay. Individually, FGF-2 and insulin failed to inhibit collagen cleavage in some OA explants whereas TGF-beta2 reduced collagen cleavage in these 5 explants and in 19 additional explants. Moreover, TGF-beta2 effectively suppressed cleavage at low concentrations. Together or individually these growth factors did not inhibit glycosaminoglycan (primarily aggrecan) degradation while TGF-beta2 occasionally did. Semiquantitative reverse transcriptase-polymerase chain reaction of articular cartilage from six OA patients revealed that TGF-beta2 suppressed expression of matrix metalloproteinase-13 and matrix metalloproteinase-9, early (PTHrP) and late (COL10A1) differentiation-related genes, and proinflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha). In contrast, TGF-beta2 up-regulated PGES-1 expression and prostaglandin E(2) release. These observations show that TGF-beta2 can suppress collagen resorption and chondrocyte differentiation in OA cartilage and that this may be mediated by prostaglandin E(2). Therefore TGF-beta2 could provide therapeutic control of type II collagen degeneration in OA.
Elena V Tchetina; John Antoniou; Michael Tanzer; David J Zukor; A Robin Poole
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of pathology     Volume:  168     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2006-01-09     Completed Date:  2006-03-23     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  131-40     Citation Subset:  AIM; IM    
Joint Diseases Laboratory, Shriners Hospitals for Children, 1529 Cedar Ave., Quebec H3G 1A6, Canada.
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MeSH Terms
Aged, 80 and over
Cartilage / drug effects,  metabolism*
Cells, Cultured
Chondrocytes / drug effects,  metabolism*,  pathology
Collagen / drug effects,  metabolism*
Dinoprostone / biosynthesis*
Enzyme-Linked Immunosorbent Assay
Fibroblast Growth Factor 2 / metabolism,  pharmacology
Gene Expression / drug effects
Glycosaminoglycans / metabolism
Insulin / metabolism,  pharmacology
Organ Culture Techniques
Osteoarthritis / drug therapy,  genetics,  metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Transforming Growth Factor beta / metabolism*,  pharmacology
Transforming Growth Factor beta2
Grant Support
2R01AG13857-05/AG/NIA NIH HHS
Reg. No./Substance:
0/Glycosaminoglycans; 0/Insulin; 0/TGFB2 protein, human; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta2; 103107-01-3/Fibroblast Growth Factor 2; 363-24-6/Dinoprostone; 9007-34-5/Collagen

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