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首页> 外文期刊>Journal of orthopaedic research >Modulation of Wnt signaling influences fracture repair.
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Modulation of Wnt signaling influences fracture repair.

机译：Wnt信号传导的调节影响骨折修复。

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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 2x/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.
机译：虽然Wnt信号在骨骼发育和体内平衡中的重要性已得到充分证明，但对其在骨折修复中的功能知之甚少。我们假设Wnt信号的激活和失活分别会增强和损害骨折修复。在Lrp5基因敲除小鼠（Lrp5-/-）和野生型同窝动物（Lrp5 + / +）以及C57BL / 6小鼠中产生了股骨骨折。 Lrp5-/-和Lrp5 + / +小鼠未经治疗，而C57BL / 6小鼠则在术后立即（第0天）或术后4天（第4天）开始接受溶媒或抗Dkk1抗体（Dkk1 Ab）治疗2x /周。每周对骨折进行射线照相，直到在第28天处死为止，然后进行DXA，pQCT和生物力学分析。与Lrp5 + / +小鼠相比，Lrp5-/-小鼠修复受损，表现为愈伤组织面积，BMC，BMD和生物力学特性降低。 Dkk1 Ab治疗的效果取决于起始时间。第0天开始增强了修复，愈伤组织面积，BMC，BMD和生物力学特性均显着提高，而第4天开始没有影响。这些结果证实了我们的假设，即Wnt信号传导会影响骨折修复，而迅速激活会增强修复，而失活则会损害骨折。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效用。

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