Activation of canonical Wnt signaling accelerates intramembranous bone regeneration in male mice.
Activation of canonical Wnt signaling accelerates intramembranous bone regeneration in male mice.
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DOI：
10.1002/jor.25217
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发表时间：
2022-08
影响因子：
2.8
通讯作者：
Sumner, D. Rick
中科院分区：
文献类型：
--
作者：
Ko, Frank C.;Moran, Meghan M.;Ross, Ryan D.;Sumner, D. Rick
典型的Wnt信号在骨骼发育、体内平衡以及软骨内和膜内修复中起重要作用。虽然研究表明抑制Wnt信号会损害膜内骨再生，但其激活如何影响膜内骨再生尚未得到充分探讨。因此，我们试图通过建立良好的骨髓消融模型来确定典型Wnt信号激活对膜内骨再生的影响。我们假设Wnt配体共受体基因Lrp5突变的小鼠会加速膜内骨再生。雄性和雌性野生型和lrp5突变小鼠在4周龄时接受右侧股骨单侧骨髓消融手术。在第3天、第5天、第7天、第10天和第14天对左股骨和右股骨进行评估。雌雄Lrp5突变小鼠的完整股骨的骨量都高于野生型小鼠，尽管雄性的骨量高于雌性。总体而言，Lrp5突变雄性小鼠的再生骨体积是同窝对照小鼠的1.8倍，而Lrp5突变雌性小鼠与同窝对照小鼠之间没有变化。此外，Lrp5突变雄性小鼠的膜内骨再生率（从第3天到第7天的差异）高于其同性同伴对照组，而雌性小鼠无差异。因此，典型Wnt信号的激活增加了两性完整骨骼的骨量，但仅在雄性小鼠中加速了损伤后的膜内骨再生。
Canonical Wnt signaling plays an important role in skeletal development, homeostasis, and both endochondral and intramembranous repair. While studies have demonstrated that the inhibition of Wnt signaling impairs intramembranous bone regeneration, how its activation affects intramembranous bone regeneration has been underexplored. Therefore, we sought to determine the effects of activation of canonical Wnt signaling on intramembranous bone regeneration by using the well-established marrow ablation model. We hypothesized that mice with a mutation in the Wnt ligand co-receptor gene Lrp5 would have accelerated intramembranous bone regeneration. Male and female wildtype and Lrp5-mutant mice underwent unilateral femoral bone marrow ablation surgery in the right femur at 4 weeks of age. Both the left intact and right operated femurs were assessed at days 3, 5, 7, 10, and 14. The intact femur of Lrp5 mutant mice of both sexes had higher bone mass than wild-type littermates, although to a greater degree in males than females. Overall, the regenerated bone volume in Lrp5 mutant male mice was 1.8-fold higher than that of littermate controls, whereas no changes were observed between female Lrp5 mutant and littermate control mice. In addition, the rate of intramembranous bone regeneration (difference from day 3 to day 7) was higher in Lrp5 mutant male mice compared to their same-sex littermate controls with no difference in the females. Thus, activation of canonical Wnt signaling increases bone mass in intact bones of both sexes, but accelerates intramembranous bone regeneration following an injury challenge only in male mice.
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影响因子：
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作者：
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DOI：
10.1002/jbmr.2900
发表时间：
2016-12
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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