title: Insulin-like growth factor I production is essential for anabolic effects of thyroid hormone in osteoblasts.
abstract: 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 3H-proline incorporation, alkaline phosphatase (ALP), and osteocalcin. Both alphaIR3, 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 3H-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.
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60611, USA.
authors.forename: B K
authors.initials: BK
authors.lastname: Huang
authors.forename: L A
authors.initials: LA
authors.lastname: Golden
authors.forename: G
authors.initials: G
authors.lastname: Tarjan
authors.forename: L D
authors.initials: LD
authors.lastname: Madison
authors.forename: P H
authors.initials: PH
authors.lastname: Stern
mesh_terms: D000818:Animals; D016723:Bone Remodeling; D002455:Cell Division; D002478:Cells, Cultured; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D015398:Signal Transduction; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D007334:Insulin-Like Growth Factor I