成骨细胞前体细胞和髓样细胞中清道夫受体的缺失不影响骨量。

Deletion of the scavenger receptor in osteoblast progenitors and myeloid cells does not affect bone mass.

作者信息

Palmieri Michela, Joseph Teenamol E, Gomez-Acevedo Horacio, Kim Ha-Neui, Manolagas Stavros C, O'Brien Charles A, Ambrogini Elena

机构信息

Division of Endocrinology and Metabolism and Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States.

Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States.

出版信息

bioRxiv. 2025 Jul 12:2025.07.09.663826. doi: 10.1101/2025.07.09.663826.

Abstract

The scavenger receptor class B member 1 (SCARB1), encoded by , is a cell surface receptor for high density lipoproteins, low density lipoproteins (LDL), oxidized LDL (OxLDL), and phosphocholine-containing oxidized phospholipids (PC-OxPLs). is expressed in multiple cell types, including osteoblasts and macrophages. PC-OxPLs, present on OxLDL and apoptotic cells, adversely affect bone metabolism. Overexpression of E06 IgM - a natural antibody that recognizes PC-OxPLs- increases cancellous and cortical bone at 6 months of age in both sexes and protects against age- and high fat diet- induced bone loss, by increasing bone formation. We have reported that is the most abundant scavenger receptor for OxPLs in osteoblastic cells, and osteoblasts derived from knockout mice ( KO) are protected from the pro- apoptotic and anti-differentiating effects of OxLDL. Skeletal analysis of KO mice produced contradictory results, with some studies reporting elevated bone mass and others reporting low bone mass. To clarify if mediates the negative effects of PC-OxPLs in bone, we deleted it in osteoblast lineage cells using Osx1-Cre transgenic mice. Bone mineral density (BMD) measurements and micro-CT analysis of cancellous and cortical bone at 6 months of age did not reveal any differences between mice and their wild-type (WT), Osx1-Cre, or littermate controls. We then investigated whether PC-OxPLs could exert their anti-osteogenic effects via activation of SCARB1 in myeloid cells by deleting in LysM-Cre expressing cells. BMD measurements and micro-CT analysis at 6 months of age did not show any differences between mice and their WT, LysM-Cre, or controls. Based on this evidence, we conclude that Based on this evidence, we conclude that the adverse skeletal effects of PC-OxPLs in adult mice are not mediated by expressed in osteoblast lineage cells or myeloid cells.

摘要

清道夫受体B类成员1(SCARB1)由[具体基因名称]编码,是一种细胞表面受体,可识别高密度脂蛋白、低密度脂蛋白(LDL)、氧化型低密度脂蛋白(OxLDL)以及含磷酸胆碱的氧化磷脂(PC-OxPLs)。它在多种细胞类型中表达,包括成骨细胞和巨噬细胞。存在于OxLDL和凋亡细胞上的PC-OxPLs对骨代谢产生不利影响。E06 IgM(一种识别PC-OxPLs的天然抗体)的过表达在6月龄时增加了两性的松质骨和皮质骨,并通过增加骨形成来预防年龄和高脂饮食诱导的骨质流失。我们曾报道,[具体基因名称]是成骨细胞中最丰富的OxPLs清道夫受体,并且源自[基因敲除小鼠名称]基因敲除小鼠([基因敲除小鼠名称] KO)的成骨细胞免受OxLDL的促凋亡和抗分化作用影响。对[基因敲除小鼠名称] KO小鼠的骨骼分析产生了相互矛盾的结果,一些研究报告骨量增加,而另一些研究报告骨量降低。为了阐明[具体基因名称]是否介导PC-OxPLs在骨中的负面影响,我们使用Osx1-Cre转基因小鼠在成骨细胞系细胞中删除了它。6月龄时的骨密度(BMD)测量以及松质骨和皮质骨的显微CT分析未显示[基因敲除小鼠名称]小鼠与其野生型(WT)、Osx1-Cre或[基因敲除小鼠名称]同窝对照之间存在任何差异。然后,我们通过在表达LysM-Cre的细胞中删除[具体基因名称]来研究PC-OxPLs是否可通过激活髓系细胞中的SCARB1发挥其抗成骨作用。6月龄时的BMD测量和显微CT分析未显示[基因敲除小鼠名称]小鼠与其WT、LysM-Cre或[基因敲除小鼠名称]对照之间存在任何差异。基于这些证据,我们得出结论,基于这些证据,我们得出结论,PC-OxPLs在成年小鼠中的不良骨骼影响不是由成骨细胞系细胞或髓系细胞中表达的[具体基因名称]介导的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccc/12265694/070c9cc13ffd/nihpp-2025.07.09.663826v1-f0001.jpg

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