花生四烯酸通过胞质磷脂酶A2依赖性途径抑制成骨细胞分化。

Arachidonic acid inhibits osteoblast differentiation through cytosolic phospholipase A2-dependent pathway.

作者信息

Yoshida K, Shinohara H, Haneji T, Nagata T

机构信息

Department of Histology and Oral Histology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto, Tokushima, Japan.

出版信息

Oral Dis. 2007 Jan;13(1):32-9. doi: 10.1111/j.1601-0825.2006.01239.x.

DOI:10.1111/j.1601-0825.2006.01239.x

PMID:17241427

Abstract

OBJECTIVE

Arachidonic acid, a precursor of prostaglandins (PGs), is released by phospholipase A2 (PLA2) and plays an important role in biological reactions. We examined the roles of arachidonic acid on the pathway of PG synthesis and osteoblast differentiation by using clone MC3T3-E1 cells.

MATERIALS AND METHODS

The effect of arachidonic acid was evaluated by the measurement of alkaline phosphatase activity, cells shape, production of arachidonic acid and the expression of cyclooxygenase (COX).

RESULTS

Arachidonic acid dose dependently decreased alkaline phosphatase activity and increased PGE2 production in MC3T3-E1 cells. The cell shape changed from polygonal to fibroblastic following treatment with arachidonic acid. These effects were recovered by the treatment of NS-398 and indomethacin. Arachidonic acid increased the expression of COX-2 mRNA and the PGE2 production. The exogenous arachidonic acid induced the release of cellular arachidonic acid in MC3T3-E1 cells. Moreover, methylarachidonyl fluorophosphonate suppressed the arachidonic acid release and the expression of COX-2 mRNA.

CONCLUSION

The present results indicate that exogenous arachidonic acid stimulated the activity of PLA2, leading to the new release of membranous arachidonic acid. The amplified arachidonic acid enhanced PGE2 production by COX-2, which inhibits the differentiation of MC3T3-E1 cells. Our results provide a new insight into the molecular mechanisms by which exogenous arachidonic acid plays a role as a paracrine/autocrine amplifier of PGE2 biosynthesis by coupling with PLA2 and COX-2.

摘要

目的

花生四烯酸是前列腺素（PGs）的前体，由磷脂酶A2（PLA2）释放，在生物反应中起重要作用。我们使用克隆的MC3T3-E1细胞研究了花生四烯酸在PG合成途径和成骨细胞分化中的作用。

材料与方法

通过测量碱性磷酸酶活性、细胞形态、花生四烯酸的产生以及环氧化酶（COX）的表达来评估花生四烯酸的作用。

结果

花生四烯酸剂量依赖性地降低MC3T3-E1细胞中的碱性磷酸酶活性并增加PGE2的产生。用花生四烯酸处理后，细胞形态从多边形变为成纤维细胞样。NS-398和吲哚美辛处理可恢复这些作用。花生四烯酸增加COX-2 mRNA的表达和PGE2的产生。外源性花生四烯酸诱导MC3T3-E1细胞中细胞内花生四烯酸的释放。此外，甲基花生四烯酰氟磷酸酯抑制花生四烯酸的释放和COX-2 mRNA的表达。

结论

目前的结果表明，外源性花生四烯酸刺激PLA2的活性，导致膜结合花生四烯酸的新释放。增加的花生四烯酸通过COX-2增强PGE2的产生，从而抑制MC3T3-E1细胞的分化。我们的结果为外源性花生四烯酸通过与PLA2和COX-2偶联作为PGE2生物合成的旁分泌/自分泌放大器发挥作用的分子机制提供了新的见解。