Modulation of Wnt signaling influences fracture repair.
Modulation of Wnt signaling influences fracture repair.
复制标题
DOI：
10.1002/jor.21078
复制
发表时间：
2010-07
影响因子：
2.8
通讯作者：
Warden, Stuart J.
中科院分区：
文献类型：
--
作者：
Komatsu, David E.;Mary, Michelle N.;Schroeder, Robert Jason;Robling, Alex G.;Turner, Charles H.;Warden, Stuart J.
虽然Wnt信号在骨骼发育和内环境稳定中的重要性已经得到了很好的证明，但关于它在骨折修复中的作用却知之甚少。我们假设Wnt信号的激活和失活分别会促进和损害骨折修复。股骨骨折发生在LRP5基因敲除小鼠(LRP5−/−)和野生型LRP5+/+小鼠(LRP5+/+)以及C57BL/6小鼠。C57BL/6小鼠于术后即刻(第0天)或术后第4天(第4天)开始注射赋形剂或抗−/−抗体(Dkk1Ab)，每周2次。骨折每周拍片，直到第28天处死，然后进行DXA、pQCT和生物力学分析。与LRP5+/+小鼠相比，LRP5−/−小鼠表现出修复受损，其骨痂面积、骨密度、骨密度和生物力学特性都有所下降。Dkk1单抗的治疗效果取决于起效时间。第0天开始促进修复，骨痂面积、BMC、BMD和生物力学性能显著增加，而第4天开始没有影响。这些结果证实了我们的假设，即Wnt信号影响骨折修复，迅速激活促进修复，失活则损害修复。此外，这些数据表明，在骨折修复过程中激活Wnt信号可能在促进骨折修复方面具有临床实用价值。
While the importance of Wnt signaling in skeletal development and homeostasis is well documented, little is known regarding its function in fracture repair. We hypothesized that activation and inactivation of Wnt signaling would enhance and impair fracture repair, respectively. Femoral fractures were generated in Lrp5 knockout mice (Lrp5−/−) and wild-type littermates (Lrp5+/+), as well as C57BL/6 mice. Lrp5−/− and Lrp5+/+mice were untreated, while C57BL/6 mice were treated 2×/week with vehicle or anti-Dkk1 antibodies (Dkk1 Ab) initiated immediately postoperatively (Day 0) or 4 days postoperatively (Day 4). Fractures were radiographed weekly until sacrifice at day 28, followed by DXA, pQCT, and biomechanical analyses. Lrp5−/− mice showed impaired repair compared to Lrp5+/+ mice, as evidenced by reduced callus area, BMC, BMD, and biomechanical properties. The effects of Dkk1 Ab treatment depended on the timing of initiation. Day 0 initiation enhanced repair, with significant gains seen for callus area, BMC, BMD, and biomechanical properties, whereas Day 4 initiation had no effect. These results validated our hypothesis that Wnt signaling influences fracture repair, with prompt activation enhancing repair and inactivation impairing it. Furthermore, these data suggest that activation of Wnt signaling during fracture repair may have clinical utility in facilitating fracture repair.
登录
查看更多内容
影响因子：
15.8
作者：
Chen Y;Whetstone HC;Lin AC;Nadesan P;Wei Q;Poon R;Alman BA
通讯作者：
Alman BA
影响因子：
4.1
作者：
Akhter, MP;Wells, DJ;Recker, RR
通讯作者：
Recker, RR
DOI：
10.1073/pnas.0505259102
发表时间：
2005-11-29
影响因子：
11.1
作者：
Clément-Lacroix, P;Ai, MR;Rawadi, G
通讯作者：
Rawadi, G
影响因子：
--
作者：
Hou, XN;Tan, Y;Das, SK
通讯作者：
Das, SK
影响因子：
64.5
作者：
Gong, YQ;Slee, RB;Warman, ML
通讯作者：
Warman, ML