Differential metabolic responses to local administration of TGF-β 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 injection of growth factors to osteoarthritic joints of aged animals. 20-month-old female ICR mice were injected with insulin-like growth factor (IGF-1), transforming growth factor-β (TGF-β) or TGF-β + IGF-1 on days 1, 4, and 7. On day 9 the joints were dissected and cultured in the presence of ³⁵S-sulfate and ³H-thymidine. Combined treatment of TGF-β and IGF-1 resulted in elevated ³H-thymidine incorporation and DNA and protein contents, reduction of ³⁵S-sulfate incorporation and alkaline phosphatase activity, with no significant change in the activity of acid phosphatase. Following injections of TGF-β, contents of DNA and protein, and incorporations of ³H-thymidine were induced, and ³⁵S-sulfate and alkaline phosphatase activity were reduced. Treatment with IGF-1 resulted in reduced incorporation of ³H-thymidine with no significant changes in the activity of acid phosphatase. Atypically hypertrophic chondrocytes were observed along the articular surface and the endogenous production of TGF-β and of IGF-1, as revealed by immunohistochemistry, was reduced. It is concluded that although ³H-thymidine incorporation and alkaline phosphatase activity appeared to be induced by TGF-β and IGF-1, the overall responsiveness of cartilage from aged mice to these growth factors appeared to be inhibitory. Moreover, their effects appeared to be limited to specific cell populations in the cartilage itself. (C) 2000 Elsevier Science Ireland Ltd.