Attenuation by incretins of thyroid hormone-stimulated osteocalcin synthesis in osteoblasts

Kainuma,Shingo; Tokuda,Haruhiko; Fujita,Kazuhiko; Kawabata,Tetsu; Sakai,Go; Matsushima‑Nishiwaki,Rie; Harada,Atsushi; Kozawa,Osamu; Otsuka,Takanobu

doi:10.3892/br.2016.798

Attenuation by incretins of thyroid hormone-stimulated osteocalcin synthesis in osteoblasts

Authors:
- Shingo Kainuma
- Haruhiko Tokuda
- Kazuhiko Fujita
- Tetsu Kawabata
- Go Sakai
- Rie Matsushima‑Nishiwaki
- Atsushi Harada
- Osamu Kozawa
- Takanobu Otsuka
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Affiliations: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan, Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan, Department of Orthopedic Surgery, National Center for Geriatrics and Gerontology, Obu, Aichi 474‑8511, Japan
Published online on: November 1, 2016 https://doi.org/10.3892/br.2016.798
Pages: 771-775

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Abstract

Incretins, the polypeptide hormone glucose‑ dependent insulinotropic polypeptide (GIP) and glucagon‑like peptide-1 (GLP-1) secreted from the small intestine after nutrient ingestion, are generally known to stimulate insulin secretion from pancreatic β-cells. We previously demonstrated that triiodothyronine (T3) stimulates osteocalcin synthesis at least in part through p38 mitogen‑activated protein kinase in osteoblast‑like MC3T3‑E1 cells. In the present study, we investigated the effects of GIP and GLP‑1 on T3‑stimulated osteocalcin synthesis and the mechanism of action involved in MC3T3‑E1 cells. GIP and GLP‑1 markedly suppressed the T3‑stimulated osteocalcin release. GIP and GLP‑1 significantly attenuated the expression levels of osteocalcin mRNA induced by T3. The T3‑stimulated transactivation activity of the thyroid hormone‑responsive element was reduced by GIP and GLP‑1. These results suggest that incretins repressed the T3‑stimulated osteocalcin synthesis in osteoblast‑like MC3T3‑E1 cells, and the suppressive effect of incretins was mediated through transcriptional levels.

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