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Article

Fluid Shear Stress Regulates Osteogenic Differentiation via AnnexinA6-Mediated Autophagy in MC3T3-E1 Cells

by
Tong Pei
†,
Guanyue Su
†,
Jie Yang
,
Wenbo Gao
,
Xinrui Yang
,
Yaojia Zhang
,
Jie Ren
,
Yang Shen
and
Xiaoheng Liu
*
Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2022, 23(24), 15702; https://doi.org/10.3390/ijms232415702
Submission received: 5 November 2022 / Revised: 30 November 2022 / Accepted: 1 December 2022 / Published: 11 December 2022
(This article belongs to the Section Molecular Biology)
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Abstract

Fluid shear stress (FSS) facilitates bone remodeling by regulating osteogenic differentiation, and extracellular matrix maturation and mineralization. However, the underlying molecular mechanisms of how mechanical stimuli from FSS are converted into osteogenesis remain largely unexplored. Here, we exposed MC3T3-E1 cells to FSS with different intensities (1 h FSS with 0, 5, 10, and 20 dyn/cm2 intensities) and treatment durations (10 dyn/cm2 FSS with 0, 0.5, 1, 2 and 4 h treatment). The results demonstrate that the 1 h of 10 dyn/cm2 FSS treatment greatly upregulated the expression of osteogenic markers (Runx2, ALP, Col I), accompanied by AnxA6 activation. The genetic ablation of AnxA6 suppressed the autophagic process, demonstrating lowered autophagy markers (Beclin1, ATG5, ATG7, LC3) and decreased autophagosome formation, and strongly reduced osteogenic differentiation induced by FSS. Furthermore, the addition of autophagic activator rapamycin to AnxA6 knockdown cells stimulated autophagy process, and coincided with more expressions of osteogenic proteins ALP and Col I under both static and FSS conditions. In conclusion, the findings in this study reveal a hitherto unidentified relationship between FSS-induced osteogenic differentiation and autophagy, and point to AnxA6 as a key mediator of autophagy in response to FSS, which may provide a new target for the treatment of osteoporosis and other diseases.
Keywords: annexinA6; fluid shear stress; autophagy; osteogenic differentiation; mineralization annexinA6; fluid shear stress; autophagy; osteogenic differentiation; mineralization

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MDPI and ACS Style

Pei, T.; Su, G.; Yang, J.; Gao, W.; Yang, X.; Zhang, Y.; Ren, J.; Shen, Y.; Liu, X. Fluid Shear Stress Regulates Osteogenic Differentiation via AnnexinA6-Mediated Autophagy in MC3T3-E1 Cells. Int. J. Mol. Sci. 2022, 23, 15702. https://doi.org/10.3390/ijms232415702

AMA Style

Pei T, Su G, Yang J, Gao W, Yang X, Zhang Y, Ren J, Shen Y, Liu X. Fluid Shear Stress Regulates Osteogenic Differentiation via AnnexinA6-Mediated Autophagy in MC3T3-E1 Cells. International Journal of Molecular Sciences. 2022; 23(24):15702. https://doi.org/10.3390/ijms232415702

Chicago/Turabian Style

Pei, Tong, Guanyue Su, Jie Yang, Wenbo Gao, Xinrui Yang, Yaojia Zhang, Jie Ren, Yang Shen, and Xiaoheng Liu. 2022. "Fluid Shear Stress Regulates Osteogenic Differentiation via AnnexinA6-Mediated Autophagy in MC3T3-E1 Cells" International Journal of Molecular Sciences 23, no. 24: 15702. https://doi.org/10.3390/ijms232415702

APA Style

Pei, T., Su, G., Yang, J., Gao, W., Yang, X., Zhang, Y., Ren, J., Shen, Y., & Liu, X. (2022). Fluid Shear Stress Regulates Osteogenic Differentiation via AnnexinA6-Mediated Autophagy in MC3T3-E1 Cells. International Journal of Molecular Sciences, 23(24), 15702. https://doi.org/10.3390/ijms232415702

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