Dkk1 haploinsufficiency requires expression of Bmp2 for bone anabolic activity.
Dkk1 haploinsufficiency requires expression of Bmp2 for bone anabolic activity.
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DOI：
10.1016/j.bone.2015.01.008
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发表时间：
2015-06
期刊：
影响因子：
4.1
通讯作者：
Nyman, Jeffry S.
中科院分区：
文献类型：
--
作者：
Intini, Giuseppe;Nyman, Jeffry S.
骨折仍然是严重的健康负担，通过增强BMP或Wnt信号可以预防和促进骨折愈合。然而，BMP和Wnt信号在合成代谢和骨折愈合活动中是必需的还是自给自足的，目前还没有完全阐明。单倍体缺乏Dkk1 （Dkk1+/−）的小鼠由于典型Wnt信号的上调而表现出高骨量表型，而四肢缺乏Bmp2表达的小鼠（Bmp2c/c;Prx1::cre）容易发生自发性骨折，并且无法启动骨折愈合；综上所述，这些小鼠提供了一个机会来研究激活BMP信号对wnt合成代谢和骨折愈合活性的要求。Dkk1+/−小鼠与Bmp2c/c杂交；Prx1::cre小鼠，携带这两种基因改变的后代不能增加骨量和愈合骨折，这表明在缺乏Bmp2的情况下，增加的典型Wnt信号无法发挥其活性。因此，我们的数据表明，BMP信号是wnt介导的合成代谢活动所必需的，旨在预防骨折和促进骨折修复的治疗可能需要针对这两种途径以获得最大疗效。
Bone fractures remain a serious health burden and prevention and enhanced healing of fractures has been obtained by augmenting either BMP or Wnt signaling. However, whether BMP and Wnt signaling are both required or are self-sufficient for anabolic and fracture healing activities has never been fully elucidated. Mice haploinsufficient for Dkk1 (Dkk1+/−) exhibit a high bone mass phenotype due to an up-regulation of canonical Wnt signaling while mice lacking Bmp2 expression in the limbs (Bmp2c/c;Prx1::cre) succumb to spontaneous fracture and are unable to initiate fracture healing; combined, these mice offer an opportunity to examine the requirement for activated BMP signaling on the anabolic and fracture healing activity of Wnts. When Dkk1+/− mice were crossed with Bmp2c/c;Prx1::cre mice, the offspring bearing both genetic alterations were unable to increase bone mass and heal fractures, indicating that increased canonical Wnt signaling is unable to exploit its activity in absence of Bmp2. Thus, our data suggest that BMP signaling is required for Wnt-mediated anabolic activity and that therapies aimed at preventing fractures and fostering fracture repair may need to target both pathways for maximal efficacy.
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