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

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...

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Main Authors: Fumiaki Makiyama, Shiori Kawase, Aoi William Omi, Yusuke Tanikawa, Taishi Kotani, Teruki Shirayama, Naoyuki Nishimura, Taiga Kurihara, Naoto Saito, Jun Takahashi, Takeshi Uemura
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Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-84176-8
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author Fumiaki Makiyama
Shiori Kawase
Aoi William Omi
Yusuke Tanikawa
Taishi Kotani
Teruki Shirayama
Naoyuki Nishimura
Taiga Kurihara
Naoto Saito
Jun Takahashi
Takeshi Uemura
author_facet Fumiaki Makiyama
Shiori Kawase
Aoi William Omi
Yusuke Tanikawa
Taishi Kotani
Teruki Shirayama
Naoyuki Nishimura
Taiga Kurihara
Naoto Saito
Jun Takahashi
Takeshi Uemura
author_sort Fumiaki Makiyama
collection DOAJ
description 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 Ca2+ 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.
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spelling doaj-art-838c8a9fd9934dbb98a70547275e3bed2025-01-05T12:23:27ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-024-84176-8Differential effects of structurally different lysophosphatidylethanolamine species on proliferation and differentiation in pre-osteoblast MC3T3-E1 cellsFumiaki Makiyama0Shiori Kawase1Aoi William Omi2Yusuke Tanikawa3Taishi Kotani4Teruki Shirayama5Naoyuki Nishimura6Taiga Kurihara7Naoto Saito8Jun Takahashi9Takeshi Uemura10Department of Orthopedic Surgery, Shinshu University School of MedicineDivision of Gene Research, Research Center for Advanced Science and Technology, Shinshu UniversityDepartment of Biomedical Engineering, Graduate School of Medicine, Science and Technology, Shinshu UniversityDepartment of Orthopedic Surgery, Shinshu University School of MedicineDepartment of Biomedical Engineering, Graduate School of Science and Technology, Shinshu UniversityDepartment of Orthopedic Surgery, Shinshu University School of MedicineInstitute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu UniversityDivision of Microbiology and Molecular Cell Biology, Nihon Pharmaceutical UniversityInstitute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu UniversityDepartment of Orthopedic Surgery, Shinshu University School of MedicineDepartment of Biomedical Engineering, Graduate School of Medicine, Science and Technology, Shinshu UniversityAbstract 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 Ca2+ 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.https://doi.org/10.1038/s41598-024-84176-8LysophosphatidylethanolaminePre-osteoblast cellProliferationDifferentiationG protein-coupled receptors
spellingShingle Fumiaki Makiyama
Shiori Kawase
Aoi William Omi
Yusuke Tanikawa
Taishi Kotani
Teruki Shirayama
Naoyuki Nishimura
Taiga Kurihara
Naoto Saito
Jun Takahashi
Takeshi Uemura
Differential effects of structurally different lysophosphatidylethanolamine species on proliferation and differentiation in pre-osteoblast MC3T3-E1 cells
Scientific Reports
Lysophosphatidylethanolamine
Pre-osteoblast cell
Proliferation
Differentiation
G protein-coupled receptors
title Differential effects of structurally different lysophosphatidylethanolamine species on proliferation and differentiation in pre-osteoblast MC3T3-E1 cells
title_full Differential effects of structurally different lysophosphatidylethanolamine species on proliferation and differentiation in pre-osteoblast MC3T3-E1 cells
title_fullStr Differential effects of structurally different lysophosphatidylethanolamine species on proliferation and differentiation in pre-osteoblast MC3T3-E1 cells
title_full_unstemmed Differential effects of structurally different lysophosphatidylethanolamine species on proliferation and differentiation in pre-osteoblast MC3T3-E1 cells
title_short Differential effects of structurally different lysophosphatidylethanolamine species on proliferation and differentiation in pre-osteoblast MC3T3-E1 cells
title_sort differential effects of structurally different lysophosphatidylethanolamine species on proliferation and differentiation in pre osteoblast mc3t3 e1 cells
topic Lysophosphatidylethanolamine
Pre-osteoblast cell
Proliferation
Differentiation
G protein-coupled receptors
url https://doi.org/10.1038/s41598-024-84176-8
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