Thyroid hormone (TH) action is mediated through two nuclear TH receptors, THRα and THRβ. While the role of THRα is well established in bone, less is known about the relevance of THRβ-mediated signaling in bone development. Based on our recent finding that TH signaling is essential for initiation and formation of secondary ossification center (SOC), we evaluated the role of THRs in mediating TH effects on epiphyseal bone formation. Two day treatment of TH deficient Tshr-/- mice with TH increased THRβ1 mRNA level at day 7 by 3.4 fold but had no effect on THRα1 mRNA level at the proximal tibia epiphysis. Treatment of serum-free cultures of tibias from 3-day old mice with T3 increased THRβ1 expression by 2.1 and 13-fold, respectively, at 24 and 72 h. Ten days treatment of Tshr-/- newborns (day 5-14) with THRβ1 agonist, GC1 at 0.2 or 2.0 µg/day increased BV/TV at day 21 by 225% and 263%, respectively, compared to vehicle treatment. Two day treatment with GC1 (0.2 µg/day) increased expression levels of Indian hedgehog by 100-fold, osterix by 15-fold and osteocalcin by 59-fold compared to vehicle at day 7 in the proximal tibia epiphysis. Gel mobility shift assay demonstrated that a putative TRE in the distal promoter of mouse Ihh gene interacted with THRβ1. GC1 treatment (1 nM) increased Ihh distal promoter activity by 20-fold after 48 hours in chondroctyes Our data suggest a novel role for THRβ1 in secondary ossification at the epiphysis that involves transcriptional upregulation of Ihh gene.
- Thyroid hormones
- Bone formation
- Indian hedge hog
- Copyright © 2016, American Journal of Physiology - Endocrinology and Metabolism