LDL uptake-dependent phosphatidylethanolamine translocation to the cell surface promotes fusion of osteoclast-like cells
LDL uptake-dependent phosphatidylethanolamine translocation to the cell surface promotes fusion of osteoclast-like cells
复制标题
DOI：
10.1242/jcs.243840
复制
发表时间：
2020-05-01
影响因子：
4
通讯作者：
Hakeda, Yoshiyuki
中科院分区：
文献类型：
--
作者：
Kitano, Victor J. F.;Ohyama, Yoko;Hakeda, Yoshiyuki
骨质疏松症与高脂血症引起的血管疾病有关，多核破骨细胞的骨吸收与脂质代谢有关。在本研究中，我们建立了低密度脂蛋白受体(LDLR)/凝集素样氧化型低密度脂蛋白受体-1(LOX-1，也称为Olr1)双基因敲除(DKO)小鼠。我们发现，与LDLR Single KO(SKO)一样，LDLR/LOX-1 dKO也阻碍破骨细胞样细胞(OCL)的细胞-细胞融合。LDLR/LOX-1dKO和LDLR sko破骨前细胞对低密度脂蛋白的摄取减少。LDLR/LOX-1dKO和LDLR sko破骨细胞表面胆固醇水平均低于野生型OCL。此外，LDLR/LOX-1dKO和LDLR sko破骨前细胞表面磷脂酰乙醇胺(PE)的数量减少，而野生型OCL的PE分布集中在与邻近细胞接触的丝状足部。取消将PE转移到细胞表面的三磷酸腺苷结合盒G1(Abcg1)转运体，导致PE转移到细胞表面和随后的细胞-细胞融合减少。本研究的结果表明，OCL的多核化过程中存在一种新的级联反应(LDLR类似于Abcg1，类似于PE转位到细胞表面，类似于细胞-细胞融合)。
Osteoporosis is associated with vessel diseases attributed to hyperlipidemia, and bone resorption by multinucleated osteoclasts is related to lipid metabolism. In this study, we generated low-density lipoprotein receptor (LDLR)/lectin-like oxidized LDL receptor-1 (LOX-1, also known as Olr1) double knockout (dKO) mice. We found that, like LDLR single KO (sKO), LDLR/LOX-1 dKO impaired cell-cell fusion of osteoclast-like cells (OCLs). LDLR/LOX-1 dKO and LDLR sKO preosteoclasts exhibited decreased uptake of LDL. The cell surface cholesterol levels of both LDLR/LOX-1 dKO and LDLR sKO osteoclasts were lower than the levels of wild-type OCLs. Additionally, the amount of phosphatidylethanolamine (PE) on the cell surface was attenuated in LDLR/LOX-1 dKO and LDLR sKO preosteoclasts, whereas the PE distribution in wild-type OCLs was concentrated on the filopodia in contact with neighboring cells. Abrogation of the ATP binding cassette G1 (ABCG1) transporter, which transfers PE to the cell surface, caused decreased PE translocation to the cell surface and subsequent cell-cell fusion. The findings of this study indicate the involvement of a novel cascade (LDLR similar to ABCG1 similar to PE translocation to cell surface similar to cell-cell fusion) in multinucleation of OCLs.