High-purity magnesium pin enhances bone consolidation in distraction osteogenesis via regulating Ptch protein activating Hedgehog-alternative Wnt signaling.
High-purity magnesium pin enhances bone consolidation in distraction osteogenesis via regulating Ptch protein activating Hedgehog-alternative Wnt signaling.
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高纯度镁针通过调节 Ptch 蛋白激活 Hedgehog-alternative Wnt 信号来增强牵引成骨过程中的骨巩固
DOI：
10.1016/j.bioactmat.2020.11.008
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发表时间：
2021-06
影响因子：
18.9
通讯作者：
Han P
中科院分区：
文献类型：
--
作者：
Hamushan M;Cai W;Zhang Y;Ren Z;Du J;Zhang S;Zhao C;Cheng P;Zhang X;Shen H;Han P
镁合金因其可降解性、成骨作用和生物相容性而成为用于骨科植入物的有前景的生物材料。镁已被证明可以促进牵引成骨。然而，其促进牵张成骨的机制尚未得到深入研究。在这项工作中，开发了一种高纯度镁针并将其应用于大鼠股骨牵引成骨。力学测试、放射学和组织学分析表明，高纯度镁针可以促进牵张成骨并缩短巩固时间。进一步的 RNA 测序研究发现替代性 Wnt 信号被激活。进一步的生物信息学分析发现Hedgehog通路是替代Wnt通路的上游信号通路。我们发现Ptch蛋白是镁的潜在靶标，并通过分子动力学证实镁离子可以与Ptch蛋白结合。总之，HP Mg 植入物在 DO 应用中具有增强骨巩固的潜力，该过程可能是通过调节 Ptch 蛋白激活 Hedgehog-替代 Wnt 信号传导来实现的。 Hp Mg 针可增强牵引成骨过程中的骨固结。 Hp Mg 激活替代 Wnt 信号传导。 Hp Mg 通过激活 Hedgehog 通路来激活替代 Wnt 信号传导。
Magnesium alloys are promising biomaterials for orthopedic implants because of their degradability, osteogenic effects, and biocompatibility. Magnesium has been proven to promote distraction osteogenesis. However, its mechanism of promoting distraction osteogenesis is not thoroughly studied. In this work, a high-purity magnesium pin developed and applied in rat femur distraction osteogenesis. Mechanical test, radiological and histological analysis suggested that high-purity magnesium pin can promote distraction osteogenesis and shorten the consolidation time. Further RNA sequencing investigation found that alternative Wnt signaling was activated. In further bioinformatics analysis, it was found that the Hedgehog pathway is the upstream signaling pathway of the alternative Wnt pathway. We found that Ptch protein is a potential target of magnesium and verified by molecular dynamics that magnesium ions can bind to Ptch protein. In conclusion, HP Mg implants have the potential to enhance bone consolidation in the DO application, and this process might be via regulating Ptch protein activating Hedgehog-alternative Wnt signaling. Hp Mg pin enhances bone consolidation in distraction osteogenesis. Hp Mg activated the alternative Wnt signaling. Hp Mg activated the alternative Wnt signaling by activating the Hedgehog pathway.
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