Abstract
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.
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Acknowledgements
This study was funded by National Natural Science Foundation of China of “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” (81560355) and “Mechanism study of bone repair mediated by rhBMP-2/rhCXCL13-loaded hollow hydroxyapatite microspheres/chitosan composite” (81560377).
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All animal studies were approved by the Jiangxi Provincial People’s Hospital Affiliated to Nanchang University and were in accordance with the Guidelines for Care and Use of Experimental Animals.
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Li, J., Xiong, S., Ding, L. et al. 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. J Mater Sci: Mater Med 30, 130 (2019). https://doi.org/10.1007/s10856-019-6340-9
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DOI: https://doi.org/10.1007/s10856-019-6340-9