Insulin-like growth factor I production is essential for anabolic effects of thyroid hormone in osteoblasts

Thyroid hormone (T3) and insulin-like growth factor I (IGF-I) are critical regulators of skeletal function. T3 increases IGF-I production in bone. To assess the potential role of IGF-I as a mediator of T3 actions, we characte rized phenotypic markers of osteoblast activity in two osteoblast models, n ormal mouse osteoblasts and MC3T3-E1 cells, exposed to T3 alone or under co nditions that interfere with IGF-I actions, T3 significantly increased oste oblast H-3-proline incorporation, alkaline phosphatase (ALP), and osteocalc in. Both alpha IR3, a neutralizing monoclonal antibody to the IGF-I recepto r, and JB1, an IGF-I analogue antagonist, attenuated the stimulatory effect s of T3, T3 effects also were decreased in cells transfected with antisense oligonucleotide (AS-ODN) to the IGF-I receptor gene. Both IGF-I and T3 had mitogenic effects that were inhibited by the antagonists. IGF-I by itself did not stimulate H-3-proline incorporation, ALP, and osteocalcin in the mo dels used, revealing that although IGF-I is essential for the anabolic effe cts of T3, it acts in concert with other factors to elicit these phenotypic responses.