Wnt/β-catenin信号通路对小鼠骨痂塑形和生物力学性能的影响

Effects of Wnt/β-catenin signals on the callus modelling and the biomechanical properties of the fractured tibia in mice

目的评价Wnt/β-catenin信号通路对骨折愈合后期骨痂塑形及其力学性能的影响。方法选择以II型胶原(Col2a1)为启动子表达ICAT(β-Catenin和TCF的抑制剂)转基因的8周龄Col2al-ICAT转基因小鼠和同窝出生野生型小鼠作为实验动物,右下肢胫骨中段截断造成实验性骨折,克氏针固定。于术后第5周进行放射学检查、常规HE染色观察以及四点弯曲生物力学测试。结果X线片显示,骨折后第5周,WT小鼠已达完全愈合;而Col2al-ICAT转基因小鼠骨折线仍模糊可见,骨折愈合不完全。组织学切片显示,骨折后第5周,WT小鼠骨折处的皮质骨连续性已基本恢复,骨皮质较厚;而Col2al-ICAT转基因小鼠骨折处皮质骨的连续性仍不完整,皮质较薄,周围可见较多编织骨存在。四点弯曲生物力学测试显示,野生型小鼠胫骨最大弯曲载荷明显优于Col2al-ICAT转基因小鼠,差异有统计学意义。结论Wnt/β-catenin信号受抑制可延缓骨痂改建的速度,从而影响骨折后生物力学性能的恢复。

Objective To evaluate the effects of Wnt/β-catenin signals on the callus modelling and the biomechanical properties of the fractured tibia in mice. Method Col2al-ICAT transgenic mice were used and ICAT transgene could specifically expressed in chondrocytes and served as a competitive inhibitor to block Wnt/β- catanin signals. 8-week-old Col2al-ICAT mice and wr littermates were used in each group and a transverse osteotomy was performed at the middle of the tibia. Fractured bones were stabilized by inserting the inner pin in the cavity. Roentgenography, histology observation and four point bending test were used to compare the callus modelling and biomechanical properties of fractured tibia between two groups 5 weeks after surgery. Result The roentgenograph revealed that the fracture repair were completed in the w-r mice while the fracture line was still visible in the Col2al-ICAT mice. Histology sections showed that there were thicker cortical bone and less woven bone in WT mice than in Col2al-ICAT transgenic mice. Four-point bending test showed that the maximum breaking load of fractured tibia in WT mice was significantly higher than in Col2al-ICAT transgenic mice. Conclusions The block of Wnt/β-catanin signals could delayed the callus modelling and then the recovery of the biomechanic properties of fractured bone.