Differential metabolic responses to local administration of TGF-beta and IGF-1 in temporomandibular joint cartilage of aged mice

Osteoarthritis is a degenerative joint disease characterized by destruction of the articular cartilage in aging and senescence. The aim of this study was to study the possible treatment of this disease by intraarticular injec tion of growth factors to osteoarthritic joints of aged animals, 20-month-o ld female ICR mice were injected with insulin-like growth factor (IGF-I). t ransforming growth factor-beta (TGF-beta) or TGF-beta + IGF-1 on days 1, 4, and 7. On day 9 the joints were dissected and cultured in the presence of S-35-sulfate and H-3-thymidine. Combined treatment of TGF-beta and IGF-1 re sulted in elevated H-3-thymidine incorporation and DNA and protein contents , reduction of S-35-sulfate incorporation and alkaline phosphatase activity , with no significant change in the activity of acid phosphatase. Following injections of TGF-beta, contents of DNA and protein, and incorporations of H-3-thymidine were induced, and S-35-sulfate and alkaline phosphatase acti vity were reduced. Treatment with IGF-I resulted in reduced incorporation o f H-3-thymidine with no significant changes in the activity of acid phospha tase. Atypically hypertrophic chondrocytes were observed along the articula r surface and the endogenous production of TGF-beta and of IGF-1, as reveal ed by immunohistochemistry, was reduced. It is concluded that although H-3- thymidine incorporation and alkaline phosphatase activity appear-ed to be i nduced by TGF-beta and IGF-1, the overall responsiveness of cartilage from aged mice to these growth factors appeared to be inhibitory. Moreover, thei r effects appeared to be limited to specific cell populations in the cartil age itself. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.