SCLEROSTIN (Sost) is expressed predominantly in osteocytes acting as a negative regulator of bone formation. In humans, mutations in the SOST gene lead to skeletal overgrowth and increased bone mineral density, suggesting that SCLEROSTIN is a key regulator of bone mass. The function of SCLEROSTIN as an inhibitor of bone formation is further supported by Sost knockout (KO) mice which display a high bone mass with elevated bone formation. Previous studies have indicated that Sost exerts its effect on bone formation through Wnt-mediated regulation of osteoblast differentiation, proliferation, and activity. Recent in vitro studies have also suggested that SCLEROSTIN regulates angiogenesis and osteoblast-to-osteocyte transition. Despite this wealth of knowledge of the mechanisms responsible for SCLEROSTIN action, no previous studies have examined whether SCLEROSTIN regulates osteocyte and vascular configuration in cortices of mouse tibia. Herein, we image tibiae from Sost KO mice and their wild-type (WT) counterparts with high-resolution CT to examine whether lack of SCLEROSTIN influences the morphometric properties of lacunae and vascular canal porosity relating to osteocytes and vessels within cortical bone. Male Sost KO and WT mice (n = 6/group) were sacrificed at 12 weeks of age. Fixed tibiae were analyzed using microCT to examine cortical bone mass and architecture. Then, samples were imaged by using benchtop and synchrotron nano-computed tomography at the tibiofibular junction. Our data, consistent with previous studies show that, Sost deficiency leads to significant enhancement of bone mass by cortical thickening and bigger cross-sectional area and we find that this occurs without modifications of tibial ellipticity, a measure of bone shape. In addition, our data show that there are no significant differences in any lacunar or vascular morphometric or geometric parameters between Sost KO mouse tibia and WT counterparts. We, therefore, conclude that the significant increases in bone mass induced by Sost deficiency are not accompanied by any significant modification in the density, organization, or shape of osteocyte lacunae or vascular content within the cortical bone. These data may imply that SCLEROSTIN does not modify the frequency of osteocytogenic recruitment of osteoblasts to initiate terminal osteocytic differentiation in mice.

中文翻译：

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Sost缺乏症不会改变小鼠的骨腔或血管孔隙。

菌素（Sost）主要在骨细胞中表达，作为骨形成的负调节剂。在人类中，SOST基因的突变会导致骨骼过度生长并增加骨矿物质密度，这表明SCLEROSTIN是骨量的关键调节剂。Sost基因敲除（KO）小鼠进一步支持了SCLEROSTIN作为骨形成抑制剂的功能，该小鼠表现出高骨量和升高的骨形成。先前的研究表明，Sost通过Wnt介导的成骨细胞分化，增殖和活性调节来发挥其对骨形成的作用。最近的体外研究还表明，胆甾醇调节血管生成和成骨细胞向成骨细胞的转变。尽管掌握了负责SCLEROSTIN动作的机制的丰富知识，以前没有研究检查过SCLEROSTIN是否能调节小鼠胫骨皮质的骨细胞和血管结构。本文中，我们用高分辨率CT对Sost KO小鼠及其野生型（WT）对应的胫骨进行成像，以检查是否缺乏SCLEROSTIN会影响与骨细胞和皮质骨内血管相关的腔隙和血管孔的形态特征。在12周龄处死雄性Sost KO和WT小鼠（n ＝ 6 /组）。使用microCT分析固定胫骨，以检查皮质骨量和结构。然后，通过台式和同步加速器纳米计算机断层摄影术在胫腓交界处对样品成像。我们的数据与以前的研究一致表明，缺乏骨灰质会导致皮质增厚和更大的横截面积，从而显着增强骨量，我们发现这种情况不会改变胫骨椭圆度（一种测量骨形）。此外，我们的数据表明，Sost KO小鼠胫骨和WT胫骨之间的任何腔隙或血管形态或几何参数均无显着差异。因此，我们得出的结论是，由Sost缺乏症引起的骨量的显着增加并未伴随着骨细胞腔的密度，组织或形状或皮质骨内血管含量的任何显着改变。这些数据可能暗示胆甾醇素不会改变成骨细胞的成骨细胞募集频率以启动小鼠的终末骨细胞分化。