AUTOCRINE PARACRINE MECHANISM OF INSULIN-LIKE GROWTH-FACTOR-I SECRETION, AND THE EFFECT OF INSULIN-LIKE GROWTH-FACTOR-I ON PROTEOGLYCAN SYNTHESIS IN BOVINE INTERVERTEBRAL DISCS/

The present study was undertaken to investigate the effect of insulin- like growth factor-1 on proteoglycan synthesis and the autocrine/parac rine mechanisms involving insulin-like growth factor-1 in the bovine c occygeal intervertebral disc. Insulin-like growth factor-1 stimulated proteoglycan synthesis in cultured cells of the nucleus pulposus of bo vine intervertebral discs in a dose-dependent manner, and the effect w as inhibited by an anti-insulin-like growth factor-1 monoclonal antibo dy. In situ hybridization histochemistry revealed the expression of in sulin-like growth factor-1 mRNA in the cultured cell, and its producti on in these cells was demonstrated by radioimmunoassay. Insulin-like g rowth factor-1 receptor in the cultured cells was also demonstrated by radioimmunoassay. Insulin-like growth factor-1 receptor in the cultur ed cells was also demonstrated immunohistochemically. Scatchard analys is using an [I-125]insulin-like growth factor-1 binding assay showed t hat the cells cultured in monolayer had a single type of insulin-like growth factor-1 receptor, whose affinity and number were estimated to be 7.38 x 10(8)/M and 9.27 x 10(4)/cell, respectively. These results s uggest that insulin-like growth factor-1 stimulates proteoglycan synth esis in cells of the nucleus pulposus and that these cells in culture have an insulin-like growth factor-1 autocrine/paracrine mechanism. Th e expressions of insulin-like growth factor-1 mRNA and insulin-like gr owth factor-1 receptor in disc tissue were greater in cells of the nuc leus pulposus of fetal bovine intervertebral discs than in those of th e adult discs. These findings suggest that the action of autocrine/par acrine insulin-like growth factor-1 is more active in cells of the you ng nucleus pulposus than in cells of mature subjects.