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 II 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-beta1 expression was shown to be depressed in strongly degraded cartilage, compared to normal and slightly altered areas. TGF-beta2 was barely detectable in all samples studied. In osteophytes, a marked overexpression of TGF-beta1 and -beta3 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-beta2 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-beta1 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-beta1 and -beta3 in osteophytes suggests that the two isoforms are involved in the formation of these structures.