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结构不同的溶血磷脂酰乙醇胺种类对成骨前体细胞MC3T3-E1增殖和分化的差异影响。

Differential effects of structurally different lysophosphatidylethanolamine species on proliferation and differentiation in pre-osteoblast MC3T3-E1 cells.

作者信息

Makiyama Fumiaki, Kawase Shiori, Omi Aoi William, Tanikawa Yusuke, Kotani Taishi, Shirayama Teruki, Nishimura Naoyuki, Kurihara Taiga, Saito Naoto, Takahashi Jun, Uemura Takeshi

机构信息

Department of Orthopedic Surgery, Shinshu University School of Medicine, Nagano, 390-8621, Japan.

Department of Biomedical Engineering, Graduate School of Medicine, Science and Technology, Shinshu University, Nagano, 390-8621, Japan.

出版信息

Sci Rep. 2025 Jan 2;15(1):466. doi: 10.1038/s41598-024-84176-8.

DOI:10.1038/s41598-024-84176-8
PMID:39747517
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11696160/
Abstract

Lysophosphatidylethanolamine (LPE) is a bioactive lipid mediator involved in diverse cellular functions. In this study, we investigated the effects of three LPE species, 1-palmitoyl LPE (16:0 LPE), 1-stearoyl LPE (18:0 LPE), and 1-oleoyl LPE (18:1 LPE) on pre-osteoblast MC3T3-E1 cells. All LPE species stimulated cell proliferation and activated the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) 1/2. MAPK/ERK1/2 activation by 16:0 LPE and 18:1 LPE was inhibited by the Gq/11 inhibitor YM-254890, while activation by 18:0 LPE was blocked by the Gi/o inhibitor pertussis toxin. Intracellular Ca transients were triggered by 16:0 LPE and 18:1 LPE but not by 18:0 LPE, with YM-254890 suppressing these responses. These results suggest that 16:0 and 18:1 LPE act via Gq/11-coupled G protein coupled receptors (GPCRs), and 18:0 LPE acts via Gi/o-coupled GPCRs. Furthermore, receptor desensitization experiments suggested that each LPE acts through distinct GPCRs. Interestingly, 18:0 LPE suppressed osteogenic differentiation, reducing mineralization, alkaline phosphatase activity, and osteogenic gene expression, whereas 16:0 LPE and 18:1 LPE had no such effects. These results suggest the physiological significance of LPEs in bone formation and indicate that different LPE species and their receptors play distinctive roles in this process.

摘要

溶血磷脂酰乙醇胺（LPE）是一种参与多种细胞功能的生物活性脂质介质。在本研究中，我们研究了三种LPE种类，即1-棕榈酰LPE（16:0 LPE）、1-硬脂酰LPE（18:0 LPE）和1-油酰LPE（18:1 LPE）对前成骨细胞MC3T3-E1细胞的影响。所有LPE种类均刺激细胞增殖并激活丝裂原活化蛋白激酶（MAPK）/细胞外信号调节激酶（ERK）1/2。16:0 LPE和18:1 LPE对MAPK/ERK1/2的激活被Gq/11抑制剂YM-254890抑制，而18:0 LPE的激活被Gi/o抑制剂百日咳毒素阻断。细胞内钙瞬变由16:0 LPE和18:1 LPE触发，但不由18:0 LPE触发，YM-254890可抑制这些反应。这些结果表明，16:0和18:1 LPE通过与Gq/11偶联的G蛋白偶联受体（GPCR）发挥作用，而18:0 LPE通过与Gi/o偶联的GPCR发挥作用。此外，受体脱敏实验表明，每种LPE通过不同的GPCR发挥作用。有趣的是，18:0 LPE抑制成骨分化，降低矿化、碱性磷酸酶活性和成骨基因表达，而16:0 LPE和18:1 LPE没有此类作用。这些结果表明LPE在骨形成中的生理意义，并表明不同的LPE种类及其受体在这一过程中发挥着独特的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9d6/11696160/2fc67203fe87/41598_2024_84176_Fig7_HTML.jpg
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