Changes in bone sclerostin levels in mice after ovariectomy vary independently of changes in serum sclerostin levels.
Changes in bone sclerostin levels in mice after ovariectomy vary independently of changes in serum sclerostin levels.
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DOI：
10.1002/jbmr.1773
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发表时间：
2013-03
影响因子：
6.2
通讯作者：
Lorenzo, Joseph
中科院分区：
文献类型：
--
作者：
Jastrzebski, Sandra;Kalinowski, Judith;Stolina, Marina;Mirza, Faryal;Torreggiani, Elena;Kalajzic, Ivo;Won, Hee Yeon;Lee, Sun-Kyeong;Lorenzo, Joseph
我们观察了卵巢摘除对8周龄假手术(Sham)或去卵巢(OVX)小鼠骨骼中硬化素mRNA和蛋白水平的影响，然后处死3或6周。后来。在这个模型中，骨丢失发生在3到5周之间。手术后。6周时，OVX组大鼠颅骨硬化素基因表达水平显著降低。术后(52%)，但在3周时没有明显效果。相比之下，3周时去卵巢大鼠股骨中硬化素mRNA水平显著降低。术后(53%)，但在术后6周与假手术组相当。OVX对硬化素的影响不是骨细胞的全局性反应，因为它们不是被另外两个相对骨细胞特异性基因：DMP-1和FGF23的mRNA水平的变化所模仿。硬化素蛋白在3wk和6wk时分别下降83%和60%。术后6周，颅骨增加38%，腰椎增加38%。在3周时，我们还检测到骨皮质细胞中硬化素的减少。手术后。而OVX在3周和6周对股骨硬化素蛋白和血清硬化素均无显著影响。手术后。这些结果表明，OVX对小鼠硬化素mRNA和蛋白的影响是不同的，这种影响取决于所检查的骨骼和手术后的时间。鉴于OVX对血清硬化素水平和不同骨骼中硬化素mRNA和蛋白水平的影响之间的差异，这些结果认为，至少在小鼠身上，血清硬化素水平可能不能准确地反映骨骼局部产生的硬化素的变化。还需要进一步的研究来评估这种情况是否也适用于人类。
We examined the effects that ovariectomy had on sclerostin mRNA and protein levels in the bones of 8-week-old mice that were either sham-operated (SHAM) or ovariectomized (OVX) and then sacrificed 3 or 6 wks. later. In this model bone loss occurred between 3 and 5 wks. Post-surgery. In calvaria OVX significantly decrease sclerostin mRNA levels at 6 wks. post-surgery (by 52%) but had no significant effect at 3 wks. In contrast, sclerostin mRNA levels were significantly lower in OVX femurs at 3 wks. post-surgery (by 53%) but equal to that of SHAM at 6 wks. The effects of OVX on sclerostin were not a global response of osteocytes since they were not mimicked by changes in the mRNA levels for 2 other relatively osteocyte-specific genes: DMP-1 and FGF-23. Sclerostin protein decreased by 83% and 60%, respectively at 3 and 6 wks. post-surgery in calvaria and by 38% in lumbar vertebrae at 6 wks. We also detected decreases in sclerostin by immunohistochemistry in cortical osteocytes of the humerus at 3 wks. post-surgery. However, there were no significant effects of OVX on sclerostin protein in femurs or on serum sclerostin at 3 and 6 wks. post-surgery. These results demonstrate that OVX has variable effects on sclerostin mRNA and protein in mice, which are dependent on the bones examined and the time after surgery. Given the discrepancy between the effects of OVX on serum sclerostin levels and sclerostin mRNA and protein levels in various bones, these results argue that, at least in mice, serum sclerostin levels may not accurately reflect changes in the local production of sclerostin in bones. Additional studies are needed to evaluate whether this is also the case in humans.
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