Immunohistochemical analysis of transforming growth factor beta isoforms and their receptors in human cartilage from normal and osteoarthritic femoral heads

Objective: Osteoarthritis (OA) is characterized by erosion of cartilage and formation of osteophytes. Since transforming growth factor beta (TGF-beta) is known to be involved in chondrogenesis and osteogenesis, we studied by immunochemistry the expression of TGF-beta isoform types 1, 2, and 3 and their receptor types I and 11 in slightly and strongly altered areas of human OA cartilage and in osteophytes. Methods: Specimens were collected from femoral heads at the time of hip arthroplasty, selecting osteophytic regions and areas of slight or severe degradation according to the Mankin score. Cryostat sections were prepared and submitted to immunohistochemistry using appropriate antibodies to TGF-beta(1-3) and TGF-beta receptors I and II. Results: TGF-beta(1) expression was shown to be depressed in strongly degraded cartilage, compared to normal and slightly altered areas. TGF-beta(2) was barely detectable in all samples studied. In osteophytes, a marked overexpression of TGF-beta(1), and -beta(3) was observed. An important decrease in TGF-beta receptor II was found in fibrillated cartilage areas. Conclusions: The three major isoforms of TGF-beta are expressed in human OA cartilage, albeit the TGF-beta(2) level is very low. Their expression patterns and the ratio of receptors I and II varies according to the degree of OA severity. The decrease in TGF-beta(1), production and marked downregulation of receptor II in fibrillated cartilage may lead to reduced chondrocyte responsiveness to TGF-beta and contribute to the irreversibility of the disease. Overexpression of TGF-beta(1), and -beta(3) in osteophytes suggests that the two isoforms are involved in the formation of these structures.