Kozawa O, Hatakeyama D, Yoshida M, Kamiya Y, Kondo C, Matsuno H, Uematsu T
Department of Pharmacology, Gifu University School of Medicine, Gifu, 500-8705, Japan.
Biochem Biophys Res Commun. 2001 Sep 7;286(5):1140-3. doi: 10.1006/bbrc.2001.5515.
It has been shown that thyroid hormone stimulates the activity of alkaline phosphatase, a marker of mature osteoblast phenotype, in osteoblasts. In the present study, we investigated whether p44/p42 mitogen-activated protein (MAP) kinase is involved in the thyroid hormone-stimulated alkaline phosphatase activity in osteoblast-like MC3T3-E1 cells. Triiodothyronine (T(3)) markedly induced the phosphorylation of p44/p42 MAP kinase. PD98059 and U0126, inhibitors of the upstream kinase that activates p44/p42 MAP kinase, significantly enhanced the T(3)-induced alkaline phosphatase activity in a dose-dependent manner. The phosphorylation of p44/p42 MAP kinase induced by T(3) was reduced by U0126. These results strongly suggest that p44/p42 MAP kinase takes part in the thyroid hormone-stimulated alkaline phosphatase activity in osteoblasts and that p44/p42 MAP kinase plays an inhibitory role in the thyroid hormone-effect.
业已表明，甲状腺激素可刺激成骨细胞中碱性磷酸酶的活性，碱性磷酸酶是成熟成骨细胞表型的一个标志物。在本研究中，我们调查了p44/p42丝裂原活化蛋白（MAP）激酶是否参与甲状腺激素刺激的成骨样MC3T3-E1细胞中的碱性磷酸酶活性。三碘甲状腺原氨酸（T3）显著诱导p44/p42 MAP激酶的磷酸化。PD98059和U0126，即激活p44/p42 MAP激酶的上游激酶的抑制剂，以剂量依赖的方式显著增强了T3诱导的碱性磷酸酶活性。U0126降低了T3诱导的p44/p42 MAP激酶的磷酸化。这些结果有力地表明，p44/p42 MAP激酶参与了甲状腺激素刺激的成骨细胞中的碱性磷酸酶活性，并且p44/p42 MAP激酶在甲状腺激素效应中起抑制作用。
