Differential up-regulation of the three TGF-{beta} isoforms in human osteoarthritic cartilage.

Autores:Manuel Pombo-Suarez, Maria Teresa Castaño-Oreja, Manuel Calaza, Juan J Gomez-Reino, Antonio Gonzalez
Idioma:ENG.
Fecha:9-5-2008
Revista:Annals of the rheumatic diseases (1468-2060)
Entrega:Ann Rheum Dis. 8 May 2008


Abstract:



OBJECTIVES:
Decreased levels of TGF-beta have been related with failure of cartilage repair in experimental models of osteoarthritis (OA). We aimed to examine this aspect of OA in human cartilage.

METHODS:
Cartilage samples were obtained from 11 patients with hip OA and 11 patients with femoral neck fracture that were undergoing total hip replacement. Gene expression of the 3 TGF-beta isoforms, collagen type II (COL2A1) and aggrecan (AGC1) was analyzed by RT-qPCR and immunohistochemistry.

RESULTS:
Expression of the three TGF-beta isoforms was increased in OA cartilage. The up-regulation was more marked for the TGF-beta3 isoform (2.3 fold) than for TGF-beta1 (1.6 fold) or TGF-beta2 (1.7 fold). The mRNA levels of TGF-beta1 and TGF-beta2 were strongly correlated in OA cartilage (rs = 0.83, p = 0.002), but levels of TGF-beta3 were uncorrelated to any of the two other TGF-beta isoforms. Immunohistochemistry showed an extension of immunoreactivity for the three TGF-beta isoforms to more chondrocytes and to deeper cartilage layers in the more severe OA lesions. No correlation of TGF- pound] isoforms with COL2A1 or AGC1 expression levels was found.

CONCLUSIONS:
The three isoforms of TGF-beta were differentially up-regulated in late OA in relation with an increased percentage of TGF-beta positive chondrocytes. These results indicate that cartilage damage progress in spite of the TGF-beta stimulus for cartilage anabolism and that other causes of the failure to cope with the increased cartilage catabolism of OA should be investigated.

Copyright:Annals of the rheumatic diseases

Hospital Clinico Universitario de Santiago, Spain.
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Annals of the rheumatic diseases