Growth hormone stimulatory effects on osteoclastic resorption are partly mediated by insulin-like growth factor I: an in vitro study.

This study investigated the possible role in vitro of insulin-like growth factor I (IGF-I) as a mediator of the effects of growth hormone (GH) on osteoclastic resorption in an unfractioned rabbit bone cell model. After 4 days of rabbit bone cell culture, human GH (hGH) (50 ng/mL) and human IGF-I (hIGF-I) (50 ng/mL) significantly increased the formation of osteoclast-like cells with a lower level than parathyroid hormone (50 ng/mL) or VD3 (10(-8) mol/L). As well as parathyroid hormone and 1-alpha,25-dihydroxyvitamin D3, addition of hGH (1, 10, and 50 ng/mL) and hIGF-I (1, 10, and 50 ng/mL) stimulated the resorption activity of osteoclasts in terms of the percentage of dentin slice surface resorbed, number of lacunae per surface unit, and mean area of lacunae as compared to the control. When neutralizing antiserum against hIGF-I (4 micrograms/mL) was added at the start of culture, the stimulatory effects of hIGF-I and hGH on osteoclastic resorption activity were totally abolished. These results indicate that the effects of GH stimulation on osteoclastic resorption in vitro are mediated via local IGF-I secretion by stromal cells such as osteoblasts. As IGF-I receptors have recently been reported on rabbit osteoclasts, a direct action of IGF-I on mature osteoclasts could be envisaged. Further experiments will be required to determine the real level of IGF-I implicated in the stimulation of bone osteoclastic resorption.