RECOMBINANT HUMAN INSULIN-LIKE GROWTH FACTOR-I STIMULATES INVITRO MATRIX SYNTHESIS AND CELL-PROLIFERATION IN RABBIT FLEXOR TENDON

Flexor tendons have an intrinsic ability for repair, with a capacity to metabolize matrix components and to proliferate. To identify factors with the potential of affecting those abilities, the effects of recombinant human insulin-like growth factor (rhIGF-I), insulin and fetal calf serum (FCS) on the synthesis of proteoglycan, collagen, and non-collagen protein and cell proliferation were investigated in short-term explant cultures of the deep flexor tendon of the rabbit. Matrix synthesis and cell proliferation were stimulated dose dependently by rhIGF-I at doses between 10 and 250 and at 10-100 ng/ml, respectively, by insulin at 250-5,000 ng/ml, and by FCS at 2-15%. Estimated maximal stimulation (E(max)) of up to three times the control value was observed with rhIGF-I at 250 ng/ml. Maximal stimulation was observed at 5,000 ng/ml with insulin, and FCS at 15%. rhIGF-I was more potent than insulin in stimulating protein synthesis and cell proliferation. The E(max) of stimulation of proteoglycan and collagen synthesis by rhIGF-I were two times that of FCS, and the E(max) of cell proliferation by FCS was twice that of rhIGF-I. Growth factors thus have the ability to stimulate matrix synthesis and cell proliferation in rabbit flexor tendon. This provides a rationale for further studies on the role of growth factors in flexor tendon healing in humans.