Bone. 2023 May;170:116702. doi: 10.1016/j.bone.2023.116702. Epub 2023 Feb 10.
The scavenger receptor class B member 1 (SR-B1 or Scarb1) is a glycosylated cell surface receptor for high density lipoproteins (HDL), oxidized low density lipoproteins (OxLDL), and phosphocholine-containing oxidized phospholipids (PC-OxPLs). Scarb1 is expressed in macrophages and has been shown to have both pro- and anti-atherogenic properties. It has been reported that global deletion of Scarb1 in mice leads to either high or low bone mass and that PC-OxPLs decrease osteoblastogenesis and increase osteoclastogenesis. PC-OxPLs decrease bone mass in 6-month-old mice and are critical pathogenetic factors in the bone loss caused by high fat diet or aging. We have investigated here whether Scarb1 expression in myeloid cells affects bone mass and whether PC-OxPLs exert their anti-osteogenic effects via activation of Scarb1 in macrophages. To this end, we generated mice with deletion of Scarb1 in LysM-Cre expressing cells and found that lack of Scarb1 did not affect bone mass in vivo. These results indicate that Scarb1 expression in cells of the myeloid/osteoclast lineage does not contribute to bone homeostasis. Based on this evidence, and earlier studies of ours showing that Scarb1 expression in osteoblasts does not affect bone mass, we conclude that Scarb1 is not an important mediator of the adverse effects on PC-OxPLs in osteoclasts or osteoblasts in 6-month-old mice.
清道夫受体 B 类成员 1(SR-B1 或 Scarb1)是一种糖基化细胞表面受体,可识别高密度脂蛋白(HDL)、氧化型低密度脂蛋白(OxLDL)和含有磷酸胆碱的氧化型磷脂(PC-OxPLs)。Scarb1 在巨噬细胞中表达,具有促动脉粥样硬化和抗动脉粥样硬化特性。有报道称,Scarb1 在小鼠中的全局缺失会导致骨量增加或减少,而 PC-OxPLs 会减少成骨细胞生成并增加破骨细胞生成。PC-OxPLs 会降低 6 月龄小鼠的骨量,并且是高脂肪饮食或衰老引起的骨丢失的关键致病因素。我们在此研究了髓系细胞中 Scarb1 的表达是否会影响骨量,以及 PC-OxPLs 是否通过激活巨噬细胞中的 Scarb1 发挥其抗成骨作用。为此,我们生成了 LysM-Cre 表达细胞中 Scarb1 缺失的小鼠,并发现 Scarb1 的缺失不会影响体内骨量。这些结果表明,髓系/破骨细胞谱系细胞中 Scarb1 的表达不会影响骨稳态。基于这一证据,以及我们之前的研究表明,成骨细胞中 Scarb1 的表达不会影响骨量,我们得出结论,Scarb1 不是 6 月龄小鼠破骨细胞或成骨细胞中 PC-OxPLs 产生不利影响的重要介质。