DIFFERENTIAL-EFFECTS OF INSULIN-LIKE GROWTH-FACTOR-I ON MATRIX AND DNA-SYNTHESIS IN VARIOUS REGIONS AND TYPES OF RABBIT TENDONS

Tendon healing and integration of tendon grafts may be site or donor s pecific. To determine if differences exist in sensitivity to growth fa ctors that have the potential to influence tendon repair, we compared the effects of recombinant human insulin-like growth factor-I on vario us types of tendon segments. The dose response effects on proteoglycan , collagen, noncollagen protein? and DNA synthesis were investigated i n short-term explant cultures of intrasynovial intermediate and proxim al segments of deep flexor tendons, extrasynovial segments of deep fle xor tendons. and Achilies tendons of rabbits. The four different types of tendon segments cultured in media without recombinant human insuli n-like growth factor-I synthesized similar amounts of each of the matr ix components. Intrasynovial proximal segments synthesized 15 times le ss DNA than other tendon segments. Recombinant human insulin-like grow th factor-I stimulated matrix and DNA synthesis of all tendon segments in a dose-dependent manner in intervals from 10 to 1,000 ng/ml. The p otency (LogED(50)) of the stimulation did not differ between the segme nts. The estimated maximal stimulation (E(max)) of proteoglycan synthe sis by recombinant human insulin-like growth factor-I was higher, and of collagen and noncollagen protein synthesis was lower, in intrasynov ial proximal segments as compared with that of the other types of segm ents. In contrast, the estimated maximal stimulation of DNA synthesis by recombinant human insulin-like growth factor-I was 6-fold higher th an controls in all types of tendons. These findings demonstrate differ ences in mitotic capacity between anatomical regions of tendons during culture without recombinant human insulin-like growth factor-I and in matrix synthesis after stimulation with it.