| First Author | Xing W | Year | 2016 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 310 |
| Issue | 10 | Pages | E846-54 |
| PubMed ID | 27026086 | Mgi Jnum | J:237084 |
| Mgi Id | MGI:5810849 | Doi | 10.1152/ajpendo.00541.2015 |
| Citation | Xing W, et al. (2016) Thyroid hormone receptor-beta1 signaling is critically involved in regulating secondary ossification via promoting transcription of the Ihh gene in the epiphysis. Am J Physiol Endocrinol Metab 310(10):E846-54 |
| abstractText | Thyroid hormone (TH) action is mediated through two nuclear TH receptors, THRalpha and THRbeta. Although the role of THRalpha is well established in bone, less is known about the relevance of THRbeta-mediated signaling in bone development. On ther basis of our recent finding that TH signaling is essential for initiation and formation of secondary ossification center, we evaluated the role of THRs in mediating TH effects on epiphysial bone formation. Two-day treatment of TH-deficient Tshr(-/-) mice with TH increased THRbeta1 mRNA level 3.4-fold at day 7 but had no effect on THRalpha1 mRNA level at the proximal tibia epiphysis. Treatment of serum-free cultures of tibias from 3-day-old mice with T3 increased THRbeta1 expression 2.1- and 13-fold, respectively, at 24 and 72 h. Ten-day treatment of Tshr(-/-) newborns (days 5-14) with THRbeta1 agonist GC1 at 0.2 or 2.0 mug/day increased BV/TV at day 21 by 225 and 263%, respectively, compared with vehicle treatment. Two-day treatment with GC1 (0.2 mug/day) increased expression levels of Indian hedgehog (Ihh) 100-fold, osterix 15-fold, and osteocalcin 59-fold compared with vehicle at day 7 in the proximal tibia epiphysis. Gel mobility shift assay demonstrated that a putative TH response element in the distal promoter of mouse Ihh gene interacted with THRbeta1. GC1 treatment (1 nM) increased Ihh distal promoter activity 20-fold after 48 h in chondroctyes. Our data suggest a novel role for THRbeta1 in secondary ossification at the epiphysis that involves transcriptional upregulation of Ihh gene. |
