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Insulin‐Like Growth Factor I Production Is Essential for Anabolic Effects of Thyroid Hormone in Osteoblasts
Author(s) -
Huang Bill K.,
Golden Laurence A.,
Tarjan Gabor,
Madison Laird D.,
Stern Paula H.
Publication year - 2000
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2000.15.2.188
Subject(s) - endocrinology , medicine , osteoblast , osteocalcin , anabolism , growth factor , insulin like growth factor , alkaline phosphatase , biology , receptor , chemistry , in vitro , biochemistry , enzyme
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 characterized phenotypic markers of osteoblast activity in two osteoblast models, normal mouse osteoblasts and MC3T3‐E1 cells, exposed to T3 alone or under conditions that interfere with IGF‐I actions. T3 significantly increased osteoblast 3 H‐proline incorporation, alkaline phosphatase (ALP), and osteocalcin. Both αIR3, a neutralizing monoclonal antibody to the IGF‐I receptor, and JB1, an IGF‐I analogue antagonist, attenuated the stimulatory effects 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 3 H‐proline incorporation, ALP, and osteocalcin in the models used, revealing that although IGF‐I is essential for the anabolic effects of T3, it acts in concert with other factors to elicit these phenotypic responses. (J Bone Miner Res 2000;15:188–197)