Wnt 信号的调节影响骨折修复。
Modulation of Wnt signaling influences fracture repair.
机构信息
InMotion Orthopaedic Research Center, 20 South Dudley, Suite 700, Memphis, Tennessee 38103, USA.
出版信息
J Orthop Res. 2010 Jul;28(7):928-36. doi: 10.1002/jor.21078.
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.
虽然 Wnt 信号在骨骼发育和稳态中的重要性已有充分的记录,但对于其在骨折修复中的作用知之甚少。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 敲除小鼠(Lrp5-/-)和野生型同窝仔(Lrp5+/+)以及 C57BL/6 小鼠中产生股骨骨折。Lrp5-/-和 Lrp5+/+小鼠未进行治疗,而 C57BL/6 小鼠在手术后立即(第 0 天)或第 4 天(第 4 天)开始每周接受 2 次载体或抗 Dkk1 抗体(Dkk1 Ab)治疗。骨折每周进行 X 光检查,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-/-小鼠的修复受损,表现为骨痂面积、BMC、BMD 和生物力学性能降低。Dkk1 Ab 治疗的效果取决于起始时间。第 0 天开始治疗可增强修复,骨痂面积、BMC、BMD 和生物力学性能均有显著提高,而第 4 天开始治疗则没有效果。这些结果验证了我们的假设,即 Wnt 信号影响骨折修复,快速激活增强修复,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 信号可能具有促进骨折修复的临床应用价值。