EFFECTS OF BASIC FIBROBLAST GROWTH-FACTOR, TRANSFORMING GROWTH-FACTOR-BETA-1, INSULIN-LIKE GROWTH-FACTOR-I, AND INSULIN ON HUMAN OSTEOARTHRITIC ARTICULAR-CARTILAGE EXPLANTS

This study evaluated the effects of basic fibroblast growth factor, tr ansforming growth factor-beta 1, insulin-like growth factor-1, and ins ulin on the incorporation of thymidine and sulfate in human osteoarthr itic articular cartilage. Tissue explants were obtained from 11 patien ts undergoing total knee arthroplasty and were categorized as nonfibri llated or fibrillated cartilage. The explants were cultured for 22 day s, with changes of medium and growth factor every 72 hours, and labele d with [H-3]thymidine and [S-35]sulfate. Growth factors were used in t he 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 insul in at 0.05, 0.5, and 5 mu g/ml. Basic fibroblast growth factor decreas ed thymidine incorporation to 70% and sulfate incorporation to less th an 20% that of the growth factor-free controls. Transforming growth fa ctor-beta 1 had no significant effect on thymidine incorporation, wher eas the concentrations studied inhibited sulfate incorporation to appr oximately 40% that of the controls. At the concentrations tested, insu lin-like growth factor-1 had no significant effect on incorporation of either thymidine or sulfate. In contrast, insulin significantly stimu lated the incorporation of both. Compared with growth factor-free cont rols, insulin maximally increased thymidine incorporation by a factor (+/-SEM) of 2.36 +/- 0.47 and 1.69 +/- 0.19 in nonfibrillated and fibr illated explants, respectively: sulfate incorporation was maximally in creased 1.60 +/- 0.24 and 1.92 +/- 0.29-fold for nonfibrillated and fi brillated explants, respectively. Of the factors tested, insulin demon strated the greatest promise for promoting a synthetic response that m ay contribute to the regeneration of osteoarthritic cartilage.