Possible involvement of p38 MAP kinase in prostaglandin E1-induced ALP activity in osteoblast-like cells

Ayako Kakita, Atsushi Suzuki, Yasunaga Ono, Yoshitaka Miura, Mitsuyasu Itoh, Yutaka Oiso

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30 Citations (Scopus)

Abstract

Prostaglandins are now recognized to be important regulators for both bone formation and resorption. Among them, prostaglandin E1 (PGE 1) has been reported to stimulate cAMP accumulation and to induce alkaline phosphatase (ALP) activity, a marker of differentiation, in osteoblast-like cells. Recently, we have shown that p38 mitogen-activated protein (MAP) kinase pathway regulates ALP activity in response to activation of Gi protein-coupled receptors in mouse osteoblast-like MC3T3-E1 cells (Suzuki et al., Endocrinology 140 (1999) 3177). In the present study, we investigated whether p38 MAP kinase is involved in ALP activation by PGE1 in MC3T3-E1 osteoblast-like cells. PGE1 dose-dependently enhanced ALP activities in the concentration range between 1 nM and 1 μM in MC3T3-E1 cells. SB203580, a specific inhibitor of p38 MAP kinase, blocked the increase in ALP activity induced by PGE1. Further analysis with western blotting suggested that PGE1 induced an increase in tyrosine (Tyr) phosphorylation of p38 MAP kinase. Both Bt2CAMP, a permeable analogue of cAMP, and forskolin, which directly activates adenylate cyclase, also induced an increase in Tyr phosphorylation of p38 MAP kinase. H-89, a potent inhibitor of protein kinase A (PKA), significantly suppressed PGE 1-induced Tyr phosphorylation of p38 MAP kinase. The results of this study suggest that PGE1 stimulates p38 MAP kinase through the activation of PKA, resulting in the enhancement of ALP activity.

Original languageEnglish
Pages (from-to)469-474
Number of pages6
JournalProstaglandins Leukotrienes and Essential Fatty Acids
Volume70
Issue number5
DOIs
Publication statusPublished - 05-2004

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Cell Biology

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