Differential up-regulation of the three TGF- isoforms in human osteoarthritic cartilage

Manuel Pombo-Suarez ¹, Maria Teresa Castaño-Oreja ², Manuel Calaza ¹, Juan J Gomez-Reino ¹ and Antonio Gonzalez ^1*

¹ Hospital Clinico Universitario de Santiago, Spain
² University of Santiago de Compostela, Spain

^* To whom correspondence should be addressed. E-mail: antonio.gonzalez.martinez-pedrayo{at}sergas.es.

Accepted 24 April 2008

Abstract

Objectives: Decreased levels of TGF- 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- isoforms, collagen type II (COL2A1) and aggrecan (AGC1) was analyzed by RT-qPCR and immunohistochemistry.

Results: Expression of the three TGF- isoforms was increased in OA cartilage. The up-regulation was more marked for the TGF-3 isoform (2.3 fold) than for TGF-1 (1.6 fold) or TGF-2 (1.7 fold). The mRNA levels of TGF-1 and TGF-2 were strongly correlated in OA cartilage (rs = 0.83, p = 0.002), but levels of TGF-3 were uncorrelated to any of the two other TGF- isoforms. Immunohistochemistry showed an extension of immunoreactivity for the three TGF- isoforms to more chondrocytes and to deeper cartilage layers in the more severe OA lesions. No correlation of TGF-£] isoforms with COL2A1 or AGC1 expression levels was found.

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