This study evaluated the effects of basic fibroblast growth factor, transforming growth factor-beta 1, insulin-like growth factor-1, and insulin on the incorporation of thymidine and sulfate in human osteoarthritic articular cartilage. Tissue explants were obtained from 11 patients undergoing total knee arthroplasty and were categorized as nonfibrillated or fibrillated cartilage. The explants were cultured for 22 days, with changes of medium and growth factor every 72 hours, and labeled with [3H]thymidine and [35S]sulfate. Growth factors were used in the following concentrations: basic fibroblast growth factor at 1, 10, and 100 ng/ml; transforming growth factor-beta 1 at 0.5, 5, and 50 ng/ml; insulin-like growth factor-1 at 0.15, 1.5, and 15 ng/ml; and insulin at 0.05, 0.5, and 5 micrograms/ml. Basic fibroblast growth factor decreased thymidine incorporation to 70% and sulfate incorporation to less than 20% that of the growth factor-free controls. Transforming growth factor-beta 1 had no significant effect on thymidine incorporation, whereas the concentrations studied inhibited sulfate incorporation to approximately 40% that of the controls. At the concentrations tested, insulin-like growth factor-1 had no significant effect on incorporation of either thymidine or sulfate. In contrast, insulin significantly stimulated the incorporation of both. Compared with growth factor-free controls, insulin maximally increased thymidine incorporation by a factor (+/- SEM) of 2.36 +/- 0.47 and 1.69 +/- 0.19 in nonfibrillated and fibrillated explants, respectively; sulfate incorporation was maximally increased 1.60 +/- 0.24 and 1.92 +/- 0.29-fold for nonfibrillated and fibrillated explants, respectively. Of the factors tested, insulin demonstrated the greatest promise for promoting a synthetic response that may contribute to the regeneration of osteoarthritic cartilage.