Tags

Type your tag names separated by a space and hit enter

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.
Am J Pathol. 2006 Jan; 168(1):131-40.AJ

Abstract

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.

Links

PMC Free PDF

Authors+Show Affiliations

Tchetina EV
Joint Diseases Laboratory, Shriners Hospitals for Children, 1529 Cedar Ave., Quebec H3G 1A6, Canada. etchetina@shriners.mcgill.ca
Antoniou J
No affiliation info available
Tanzer M
No affiliation info available
Zukor DJ
No affiliation info available
Poole AR
No affiliation info available

MeSH

AgedAged, 80 and overCartilageCells, CulturedChondrocytesCollagenDinoprostoneEnzyme-Linked Immunosorbent AssayFemaleFibroblast Growth Factor 2Gene ExpressionGlycosaminoglycansHumansInsulinMaleOrgan Culture TechniquesOsteoarthritisReverse Transcriptase Polymerase Chain ReactionTransforming Growth Factor betaTransforming Growth Factor beta2

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16400016

Citation

Tchetina, Elena V., et al. "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." The American Journal of Pathology, vol. 168, no. 1, 2006, pp. 131-40.
Tchetina EV, Antoniou J, Tanzer M, et al. 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. Am J Pathol. 2006;168(1):131-40.
Tchetina, E. V., Antoniou, J., Tanzer, M., Zukor, D. J., & Poole, A. R. (2006). 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. The American Journal of Pathology, 168(1), 131-40.
Tchetina EV, et al. 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. Am J Pathol. 2006;168(1):131-40. PubMed PMID: 16400016.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Tchetina,Elena V, AU - Antoniou,John, AU - Tanzer,Michael, AU - Zukor,David J, AU - Poole,A Robin, PY - 2006/1/10/pubmed PY - 2006/3/24/medline PY - 2006/1/10/entrez SP - 131 EP - 40 JF - The American journal of pathology JO - Am J Pathol VL - 168 IS - 1 N2 - 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. SN - 0002-9440 UR - https://www.unboundmedicine.com/medline/citation/16400016/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_ DB - PRIME DP - Unbound Medicine ER -