Activation of p38 mitogen-activated protein kinase mediates thyroid hormone-stimulated osteocalcin synthesis in osteoblasts

It is well known that thyroid hormone modulates osteoblast cell function. We have previously shown that triiodothyronine (T 3) activates p44/p42 mitogen-activated protein (MAP) kinase, which limits T 3-induced alkaline phosphatase activity in osteoblast-like MC3T3-E1 cells. In the present study, we...

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Bibliographic Details
Published in:Molecular and cellular endocrinology 2004-02, Vol.214 (1), p.189-195
Main Authors: Ishisaki, A., Tokuda, H., Yoshida, M., Hirade, K., Kunieda, K., Hatakeyama, D., Shibata, T., Kozawa, O.
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Cells, Cultured
Enzyme Inhibitors - pharmacology
Kinetics
Mice
Mitogen-activated protein kinase
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases - metabolism
Mitogen-Activated Protein Kinases - physiology
Myelin Basic Protein - metabolism
Osteoblasts
Osteoblasts - metabolism
Osteocalcin
Osteocalcin - biosynthesis
p38 Mitogen-Activated Protein Kinases
Phosphorylation - drug effects
Thyroid hormone
Triiodothyronine - pharmacology
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Summary:It is well known that thyroid hormone modulates osteoblast cell function. We have previously shown that triiodothyronine (T 3) activates p44/p42 mitogen-activated protein (MAP) kinase, which limits T 3-induced alkaline phosphatase activity in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether p44/p42 MAP kinase or p38 MAP kinase is involved in the thyroid hormone-stimulated osteocalcin synthesis in these cells. T 3 markedly induced the phosphorylation of p38 MAP kinase in addition to p44/p42 MAP kinase. PD98059 and U0126, inhibitors of the upstream kinase that activates p44/p42 MAP kinase, had little effect on the T 3-induced synthesis of osteocalcin. On the contrary, the T 3-induced osteocalcin synthesis was significantly reduced by SB203580 and PD169316, inhibitors of p38 MAP kinase. SB203580, PD169316 or PD98059 suppressed the T 3-phosphorylation of myelin basic protein. T 3-induced osteocalcin synthesis was significantly reduced by SB203580 or PD169316 also in primary cultured mouse osteoblasts. These results strongly suggest that p38 MAP kinase but not p44/p42 MAP kinase takes part in the thyroid hormone-stimulated osteocalcin synthesis in osteoblasts.
ISSN:0303-7207
1872-8057
DOI:10.1016/j.mce.2003.10.049