TGF β-induced cartilage repair is maintained but fibrosis is blocked in the presence of Smad7

Cartilage damage in osteoarthritis (OA) is considered an imbalance between catabolic and anabolic factors, favoring the catabolic side. We assessed whether adenoviral overexpression of transforming growth factor-beta (TGF beta) enhanced cartilage repair and whether TGF beta-induced fibrosis was blocked by local expression of the intracellular TGF beta inhibitor Smad7. We inflicted cartilage damage by injection of interleukin-1 (IL-1) into murine knee joints. After 2 days, we injected an adenovirus encoding TGF beta. On day 4, we measured proteoglycan ( PG) synthesis and content. To examine whether we could block TGF beta-induced fibrosis and stimulate cartilage repair simultaneously, we injected Ad-TGF beta and Ad-Smad7. This was performed both after IL-1-induced damage and in a model of primary OA. In addition to PG in cartilage, synovial fibrosis was measured by determining the synovial width and the number of procollagen I-expressing cells. Adenoviral overexpression of TGF beta restored the IL-1-induced reduction in PG content and increased PG synthesis. TGF beta-induced an elevation in PG content in cartilage of the OA model. TGF beta induced synovial fibrosis was strongly diminished by simultaneous synovial overexpression of Smad7 in the synovial lining. Of great interest, overexpression of Smad7 did not reduce the repair-stimulating effect of TGF beta on cartilage. Adenoviral overexpression of TGF beta stimulated repair of IL-1- and OA-damaged cartilage. TGF beta-induced synovial fibrosis was blocked by locally inhibiting TGF beta signaling in the synovial lining by simultaneously transfecting it with an adenovirus overexpressing Smad7.