Differential upregulation of the three transforming growth factor beta isoforms in human osteoarthritic cartilage

Objectives: Decreased levels of transforming growth factor beta (TGF beta) have been related to the failure of cartilage repair in experimental models of osteoarthritis. This study aimed to examine this aspect of osteoarthritis in human cartilage. Methods: Cartilage samples were obtained from 11 patients with hip osteoarthritis and 11 patients with femoral neck fracture who were undergoing total hip replacement. Gene expression of the three TGF beta isoforms, collagen type II (COL2A1) and aggrecan (AGC1) was analysed by reverse transcription quantitative PCR and immunohistochemistry. Results: Expression of the three TGF beta isoforms was increased in osteoarthritis cartilage. The upregulation was more marked for the TGF beta 3 isoform (2.3-fold) than for TGF beta 1 (1.6-fold) or TGF beta 2 (1.7-fold). The messenger RNA levels of TGF beta 1 and TGF beta 2 were strongly correlated in osteoarthritis cartilage (r(s) = 0.83, p = 0.002), but levels of TGF beta 3 were uncorrelated with 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 osteoarthritis lesions. No correlation of TGF beta isoforms with COL2A1 or AGC1 expression levels was found. Conclusions: The three isoforms of TGF beta were differentially upregulated in late osteoarthritis in relation to an increased percentage of TGF beta-positive chondrocytes. These results indicate that cartilage damage progresses 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 osteoarthritis should be investigated.