Effect of transforming growth factor (TGF)-beta deprivation on intrinsic cartilage repair capacity. Murine knee joints of young mice were injected with IL-1. After two days an adenovirus expressing the TGF-beta inhibitor latency associated peptide (LAP) was injected intra-articularly. Four days after the initial injections with IL-1, patellae were isolated for 35S-sulfate incorporation and whole knee joints were isolated for histology. (a) 35S-sulfate incorporation into isolated patellar cartilage after treatment with IL-1 and Ad-LAP. IL-1 treatment induces an initial decrease in 35S-sulfate incorporation, but by day 4 the 35S-sulfate incorporation increased above normal levels, indicating an overshoot in proteoglycan synthesis. By blocking endogenous TGF-beta with LAP, this overshoot is completely abolished. (b) Proteoglycan content of patellar cartilage after treatment with IL-1 and Ad-LAP. IL-1 injection results in depletion of proteoglycans in cartilage. Blocking endogenous TGF-beta with LAP results in an aggravation of this depletion beyond IL-1 induced damage alone.