The role of autonomously secreted PGE2 and its autocrine/paracrine effect on bone matrix mineralization at the different stages of differentiating MC3T3-E1 cells
The role of autonomously secreted PGE2 and its autocrine/paracrine effect on bone matrix mineralization at the different stages of differentiating MC3T3-E1 cells
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DOI：
10.1016/j.bbrc.2020.01.120
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发表时间：
2020-04-16
影响因子：
3.1
通讯作者：
Izumi, Takashi
中科院分区：
文献类型：
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作者：
Suzuki, Hiraku;Ohshima, Noriyasu;Izumi, Takashi
骨由成骨细胞系细胞、处于不同分化阶段的骨形成细胞组成。然而，目前尚不完全了解这些从骨髓迁移的细胞如何沟通和相互作用。在本研究中，我们证明前列腺素 E2 (PGE(2)) 在成骨细胞系 MC3T3-E1 基质矿化的自主修饰以及不同分化阶段细胞之间的相互作用中发挥作用。使用 LC-MS/MS 和抑制剂的分析显示，分化阶段的前列腺素类化合物中 PGE(2) 的自主分泌取决于 COX-2，这是一个关键因素。 用于生产 PGE(2) 的酶。用 PGE(2) 受体和 COX-2 抑制剂治疗表明，分泌的 PGE(2) 以自分泌/旁分泌方式调节基质矿化。此外，我们发现PGE(2)受体(EP1-EP4)的表达谱以及PGE(2)对基质矿化的影响在细胞分化过程中发生变化。在MC3T3-E1细胞的早期分化阶段用PGE(2)信号抑制剂进行处理，几天后诱导了基质矿化的显着变化。用包含PGE(2)的成熟细胞培养基提取物刺激并与分泌PGE(2)的成熟细胞共培养可显着促进早期细胞的基质矿化，相反，用COX-2和PGE(2)受体抑制剂处理则不能。这些结果支持PGE(2)在骨组织中成骨细胞-谱系细胞相互作用系统中发挥重要作用，以调节反映骨形成细胞状况（即群体和成熟）的基质矿化。 (C) 2020 Elsevier Inc. 保留所有权利。
Bone is consisted of osteoblast-linage cells, bone-forming cells in various differentiation stages. However, it is not fully understood how communicate and interact these cells immigrated from bone marrow. In this study, we showed that prostaglandin E2 (PGE(2)) had a role in autonomous modification of matrix mineralization in osteoblastic cell line, MC3T3-E1, and interactions across the cells in different differentiation stages.Analysis using LC-MS/MS and inhibitors showed the autonomous secretion of PGE(2) among the prostanoids in differentiation stages and that depend on COX-2, a key enzyme for production of PGE(2). Treatment with inhibitors of PGE(2) receptors and COX-2 indicated that secreted PGE(2) regulates matrix mineralization in an autocrine/paracrine manner. In addition, we showed that the expression profile of PGE(2) receptors (EP1-EP4) and PGE(2) effects on matrix mineralization derived from it changed during cell differentiation.Treatment with inhibitors of PGE(2) signaling in the early differentiation stage of MC3T3-E1 cells induced significant changes in matrix mineralization several days after. Stimulation with the extracts from culture medium of the matured cells including PGE(2) and co-culture with the matured cells secreting PGE(2) significantly promoted matrix mineralization of the early stage cells, in contrast, treatment with inhibitor of COX-2 and PGE(2) receptors failed to do so. These results support that PGE(2) plays important roles in the interaction system of osteoblast-linage cells in bone tissue to regulate matrix mineralization reflecting condition of bone-forming cells, that is, population and maturation. (C) 2020 Elsevier Inc. All rights reserved.