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

• Published in: Molecular and cellular endocrinology Vol. 214; no. 1; pp. 189 - 195
• Main Authors: Ishisaki, A., Tokuda, H., Yoshida, M., Hirade, K., Kunieda, K., Hatakeyama, D., Shibata, T., Kozawa, O.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 12.02.2004
• 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; Mitogen-activated protein kinase; Thyroid hormone; Osteocalcin; Osteoblasts
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2003.10.049

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.