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ID 112352
Irie, Atsushi Tokyo Metropolitan Institute of Medical Science
Yamamoto, Kei Tokyo Metropolitan Institute of Medical Science|Tokushima University|Japan Agency for Medical Research and Development Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Miki, Yoshimi Tokyo Metropolitan Institute of Medical Science
Murakami, Makoto Tokyo Metropolitan Institute of Medical Science|Japan Agency for Medical Research and Development
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Journal Article
Osteoclasts, responsible for bone resorption, are multinucleated cells formed by cell-cell fusion of mononuclear pre-osteoclasts. Although osteoclast fusion is a pivotal step for osteoclastogenesis, little is known about the mechanism involved. To clarify the underlying process, we investigated dynamics of membrane phospholipids during osteoclastogenesis in vitro. We found that the cellular content of phospholipids, phosphatidylethanolamine (PE) in particular, was increased during osteoclast differentiation. Furthermore, PE was greatly increased in the outer leaflet of the plasma membrane bilayer during osteoclastogenesis, being concentrated in filopodia involved in cell-cell fusion. Immobilisation of the cell surface PE blocked osteoclast fusion, revealing the importance of PE abundance and distribution. To identify the molecules responsible for these PE dynamics, we screened a wide array of lipid-related genes by quantitative PCR and shRNA-mediated knockdown. Among them, a PE-biosynthetic enzyme, acyl-CoA:lysophosphatidylethanolamine acyltransferase 2 (LPEAT2), and two ATP-binding cassette (ABC) transporters, ABCB4 and ABCG1, were markedly increased during osteoclastogenesis, and their knockdown in pre-osteoclasts led to reduction in PE exposure on the cell surface and subsequent osteoclast fusion. These findings demonstrate that the PE dynamics play an essential role in osteoclast fusion, in which LPEAT2, ABCB4 and ABCG1 are key players for PE biosynthesis and redistribution.
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Scientific Reports
Springer Nature
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Supplementary File : srep_7_46715_s1.pdf
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Bioscience and Bioindustry