Wnt3a downregulates thyroid hormone‑induced osteocalcin expression in osteoblasts

Fujita,Kazuhiko; Otsuka,Takanobu; Kawabata,Tetsu; Sakai,Go; Kim,Woo; Matsushima‑Nishiwaki,Rie; Kozawa,Osamu; Tokuda,Haruhiko

doi:10.3892/etm.2019.7764

Wnt3a downregulates thyroid hormone‑induced osteocalcin expression in osteoblasts

Authors:
- Kazuhiko Fujita
- Takanobu Otsuka
- Tetsu Kawabata
- Go Sakai
- Woo Kim
- Rie Matsushima‑Nishiwaki
- Osamu Kozawa
- Haruhiko Tokuda
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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
Published online on: July 10, 2019 https://doi.org/10.3892/etm.2019.7764
Pages: 1921-1927

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Abstract

Wnt3a is a crucial modulator of bone metabolism through the canonical Wnt/β‑catenin signaling pathway in bone‑forming osteoblasts. We previously reported that the expression of osteocalcin is stimulated by triiodothyronine (T3) at least in part through the activation of p38 mitogen‑activated protein (MAP) kinase but not p44/p42 MAP kinase in osteoblast‑like MC3T3‑E1 cells. In the present study, we investigated the effect of Wnt3a on the T3‑induced osteocalcin expression in these cells. Wnt3a suppressed the release of osteocalcin induced by T3. The inhibitory effect of Wnt3a was dose‑dependent between 0.3 and 30 ng/ml. SB216763, an inhibitor of glycogen synthase kinase‑3β, that reduces the phosphorylation of β‑catenin, inhibited the T3‑induced osteocalcin release. Wnt3a, as well as SB216763, reduced the expression of osteocalcin mRNA induced by T3. The transcriptional activity induced by T3, assessed by a luciferase activity, was also suppressed by both Wnt3a and SB216763. In contrast, Wnt3a did not markedly affect the T3‑stimulated phosphorylation of p38 MAP kinase. These results suggested that Wnt3a downregulates the T3‑stimulated osteocalcin expression in MC3T3‑E1 cells, and the suppressive effect of Wnt3a is independent of p38 MAP kinase.

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