Scavenger receptor class B, type I (Scarb1) deficiency promotes osteoblastogenesis but stunts terminal osteocyte differentiation.
Scavenger receptor class B, type I (Scarb1) deficiency promotes osteoblastogenesis but stunts terminal osteocyte differentiation.
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DOI：
10.14814/phy2.12117
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发表时间：
2014-10-01
影响因子：
2.5
通讯作者：
Moreau R
中科院分区：
文献类型：
--
作者：
Martineau C;Kevorkova O;Brissette L;Moreau R
清道夫受体BI型(SR-BI)是Scar1基因产物，是一种高密度脂蛋白(HDLR)受体，可影响骨代谢。在小鼠中，它的缺失与糖皮质激素/促肾上腺皮质激素轴的变化有关，并转化为高骨量和增强骨形成。由于骨形成增强背后的细胞变化尚不清楚，我们在体外研究了SCA1缺陷的骨髓基质细胞(MSC)的行为。SCA1缺失和野生型(WT)细胞在高密度脂蛋白(HDL3)、胆固醇(CE)或雌二醇(E)结合/结合方面没有差异。成骨治疗后，Scar1基因的表达下调两倍。HDL3暴露对WT和Null细胞的增殖均无影响，但这一条件降低了成骨细胞标志物Osterix(SP7)、骨细胞标志物硬化素(Sost)和牙本质基质蛋白1(Dmp1)的基因表达，而不受基因型的影响。空细胞中SOST和Dmp1的基础表达分别是WT细胞的40%和50%；相应地，Scar1基因缺失小鼠椎骨中的骨细胞密度降低了20%。Wnt信号的辅助受体，即低密度脂蛋白相关蛋白(Lrp)5和Lrp8的基因表达分别增加了2倍和3倍，转录靶基因轴抑制蛋白2(Axin2)和淋巴增强因子1(Lef1)的基因表达增加了3倍以上。Wnt信号激动剂Wnt5a和拮抗剂dickkopff相关蛋白1(Dkk1)的基因表达在Null MSC中增加了10-20倍。这些数据表明，在SCA1缺乏的MSC中，Wnt通路的变化可能解释了它们功能的增强，从而导致了在这些小鼠中观察到的高骨量。Scar1缺乏转化为高骨量和促进骨形成。我们研究了Scar1缺陷的骨髓基质细胞(MSC)在体外的行为。我们的结果表明，在SCA1缺乏的MSC中，Wnt通路的变化可能解释了它们功能的增强，从而导致了在这些小鼠中观察到的高骨量。
Scavenger receptor class B type I (SR‐BI), the Scarb1 gene product, is a high‐density lipoprotein (HDL) receptor which was shown to influence bone metabolism. Its absence in mice is associated with alterations of the glucocorticoid/adrenocorticotropic hormone axis, and translated in high bone mass and enhanced bone formation. Since the cellular alterations underlying the enhanced bone formation remain unknown, we investigated Scarb1‐deficient marrow stromal cells (MSC) behavior in vitro. No difference in HDL3, cholesteryl ester (CE) or estradiol (E) association/binding was measured between Scarb1‐null and wild‐type (WT) cells. Scarb1 genic expression was down‐regulated twofold following osteogenic treatment. Neither WT nor null cell proliferation was influenced by HDL3 exposure whereas this condition decreased genic expression of osteoblastic marker osterix (Sp7), and osteocyte markers sclerostin (Sost) and dentin matrix protein 1 (Dmp1) independently of genotype. Sost and Dmp1 basal expression in null cells was 40% and 50% that of WT cells; accordingly, osteocyte density was 20% lower in vertebrae from Scarb1‐null mice. Genic expression of co‐receptors for Wnt signaling, namely LDL‐related protein (Lrp) 5 and Lrp8, was increased, respectively, by two‐ and threefold, and of transcription target‐genes axis inhibition protein 2 (Axin2) and lymphoid enhancer‐binding factor 1 (Lef1) over threefold. Gene expression of Wnt signaling agonist Wnt5a and of the antagonist dickkopfs‐related protein 1 (Dkk1) were found to be increased 10‐ to 20‐fold in null MSC. These data suggest alterations of Wnt pathways in Scarb1‐deficient MSC potentially explaining their enhanced function, hence contributing to the high bone mass observed in these mice. Scarb1‐deficiency translated in high bone mass and enhanced bone formation. We investigated Scarb1‐deficient marrow stromal cells (MSC) behavior in vitro. Our results suggest alterations of Wnt pathways in Scarb1‐deficient MSC potentially explaining their enhanced function, hence contributing to the high bone mass observed in these mice.