The mechanism research of non-Smad dependent TAK1 signaling pathway in the treatment of bone defects by recombination BMP-2- loaded hollow hydroxyapatite microspheres/chitosan composite
The mechanism research of non-Smad dependent TAK1 signaling pathway in the treatment of bone defects by recombination BMP-2- loaded hollow hydroxyapatite microspheres/chitosan composite
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非Smad依赖性TAK1信号通路重组BMP-2负载空心羟基磷灰石微球/壳聚糖复合材料治疗骨缺损的机制研究
DOI：
10.1007/s10856-019
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
xionglong
中科院分区：
文献类型：
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作者：
xionglong
目的探讨非Smad依赖的TAK 1信号通路（BMP-2-TAK 1-p38-.Osx信号通路）在中空羟基磷灰石（HA）微球/壳聚糖（CS）复合材料介导的骨修复中的作用。方法首先研究复合物中rhBMP-2的生物学活性。然后进行成骨细胞分化试验，包括碱性磷酸酶活性、钙沉积、X线评分和三点弯曲试验。采用逆转录-聚合酶链反应（RT-PCR）检测TAK 1、p38、Osx及成骨标志物的mRNA表达。结果rhBMP-2可从复合物中以生物活性形式负载并释放。此外，与HA/CS支架相比，复合物提供了延长的时间段。TAK 1抑制剂组和p38抑制剂组血清ALP活性明显降低。X线片显示rhBMP-2空心HA微球/CS复合材料组可见骨痂形成。在三点弯曲试验中，p38抑制剂组的负荷值降低。在动物模型中，p38抑制剂组和TAK1.1抑制剂组在第90天BSP mRNA表达显著降低。在MC 3 T3-E1细胞中，rhBMP-2组和rhBMP-2空心HA微球/CS复合物组OSX mRNA表达明显上调，而TAK 1抑制剂组和p38抑制剂组OSX mRNA表达明显下调。结论rhBMP-2中空HA微球/CS复合材料介导的BMP-2-TAK 1-p38-OSX信号通路可能在骨形成和修复中发挥重要作用。
Aims The present study aimed to evaluate whether the non-Smad dependent TAK1 signaling pathway (BMP-2-TAK1-p38-.Osx signaling pathway) played an important role in bone repair mediated by hollow hydroxyapatite (HA) microspheres/.chitosan (CS) composite..Methods Firstly, the biological activity of rhBMP-2 released from the complex was investigated. Then, differentiation test.of osteoblasts including ALP activity and calcium deposition, X-ray scoring and three-point bending test were performed..Finally, the mRNAs expression of TAK1, p38, Osx and osteogenic markers was tested by reverse transcription-polymerase.chain reaction (RT-PCR)..Results RhBMP-2 could be loaded and released from the complex in bioactive form. Additionally, the complex provided a.prolonged period of time compared with HA/CS scaffolds. Serum ALP activity was significantly decreased in the TAK1.inhibitor group and p38 inhibitor group. In the X-ray radiography, bone callus was observed in rhBMP-2-loaded hollow HA.microspheres/CS composite group. In the three-point bending test, load values in p38 inhibitor group decreased. In the.animal model, the mRNA expression of BSP on day 90 was significantly decreased in the p38 inhibitor group and TAK1.inhibitor group. In MC3T3-E1 cells, the mRNA expression of OSX was remarkably up-regulated in both rhBMP-2 group or.rhBMP-2-loaded hollow HA microspheres/CS composite group; while the mRNA expression of OSX was significantly.down-regulated in TAK1 inhibitor group and p38 inhibitor group..Conclusion The BMP-2-TAK1-p38-OSX signaling pathway may play an important role in bone formation and repair.mediated by rhBMP-2-loaded hollow HA microspheres/CS composite.