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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >Cholesterol-sensing receptors, liver X receptor alpha and beta, have novel and distinct roles in osteoclast differentiation and activation.
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Cholesterol-sensing receptors, liver X receptor alpha and beta, have novel and distinct roles in osteoclast differentiation and activation.

机译：胆固醇感应受体，肝脏X受体α和β，在破骨细胞的分化和激活中具有新颖而独特的作用。

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The liver X receptor (alpha,beta) is responsible for regulating cholesterol homeostasis in cells. However, our studies using the LXRalpha-/-, LXRbeta-/-, and LXRalpha-/-beta-/- mice show that both LXRalpha and beta are also important for bone turnover, mainly by regulating osteoclast differentiation/activity. Introduction: The liver X receptors (alpha,beta) are primarily responsible for regulating cholesterol homeostasis within cells and the whole body. However, as recent studies show that the role for this receptor is expanding, we studied whether the LXRs could be implicated in bone homeostasis and development. MATERIALS AND METHODS: pQCT was performed on both male and female LXRalpha-/-, LXRbeta-/-, LXRalpha-/-beta-/-, and WT mice at 4 months and 1 year of age. Four-month-old female mice were additionally analyzed with reference to qPCR, immunohistochemistry, histomorphometry, transmission electron microscopy, and serum bone turnover markers. RESULTS: At the mRNA level, LXRbeta was more highly expressed than LXRalpha in both whole long bones and differentiating osteoblast-like MC3T3-E1 and osteoclast-like RAW 264.7 cells. Four-month-old female LXRalpha-/- mice had a significant increase in BMD because of an increase in all cortical parameters. No difference was seen regarding trabecular BMD. Quantitative histomorphometry showed that these mice had significantly more endosteal osteoclasts in the cortical bone; however, these cells appeared less active than normal cells as suggested by a significant reduction in serum levels of cross-linked carboxyterminal telopeptides of type I collagen (CTX) and a reduction in bone TRACP activity. Conversely, the female LXRbeta-/- mice exhibited no change in BMD, presumably because a significant decline in the number of the trabecular osteoclasts was compensated for by an increase in the expression of the osteoclast markers cathepsin K and TRACP. These mice also had a significant decrease in serum CTX, suggesting decreased bone resorption; however, in addition presented with an increase in the expression of osteoblast associated genes, bone formation markers, and serum leptin levels. CONCLUSIONS: Our findings show that both LXRs influence cellular function within the bone, with LXRalpha having an impact on osteoclast activity, primarily in cortical bone, whereas LXRbeta modulates trabecular bone turnover.
机译：肝脏X受体（alpha，beta）负责调节细胞中胆固醇的体内稳态。但是，我们使用LXRalpha-/-，LXRbeta-/-和LXRalpha-/-beta-/-小鼠进行的研究表明，LXRalpha和beta对骨骼更新也很重要，主要是通过调节破骨细胞的分化/活性。简介：肝脏X受体（α，β）主要负责调节细胞和整个体内的胆固醇稳态。但是，由于最近的研究表明该受体的作用正在扩大，因此我们研究了LXR是否可能与骨稳态和发育有关。材料与方法：在4个月和1岁大的雄性和雌性LXRalpha-/-，LXRbeta-/-，LXRalpha-/-beta-/-和WT小鼠上进行pQCT。参照qPCR，免疫组织化学，组织形态学，透射电镜和血清骨转换标志物，另外对4个月大的雌性小鼠进行了分析。结果：在mRNA水平上，LXRbeta在整个长骨以及分化成骨样MC3T3-E1和破骨细胞样RAW 264.7细胞中的表达均高于LXRalpha。四个月大的雌性LXRalpha-/-小鼠的BMD显着增加，因为所有皮质参数均增加。小梁骨密度无差异。定量组织形态计量学显示，这些小鼠的皮质骨中有大量的骨内破骨细胞。但是，这些细胞的活性似乎比正常细胞低，这是由于I型胶原（CTX）交联的羧基末端端肽的血清水平显着降低和骨骼TRACP活性降低所表明的。相反，雌性LXRbeta-/-小鼠的BMD没有变化，可能是由于破骨细胞标志物组织蛋白酶K和TRACP表达的增加补偿了小梁破骨细胞数量的显着下降。这些小鼠的血清CTX也明显降低，表明骨吸收降低。然而，此外，成骨细胞相关基因，骨形成标志物和血清瘦素水平的表达增加。结论：我们的研究结果表明，两种LXR都会影响骨骼内的细胞功能，LXRalpha会对破骨细胞活性（主要是在皮质骨中）产生影响，而LXRbeta会调节小梁骨转换。

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