Cargando…

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

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 e...

Descripción completa

Detalles Bibliográficos
Autores principales: Pei, Tong, Su, Guanyue, Yang, Jie, Gao, Wenbo, Yang, Xinrui, Zhang, Yaojia, Ren, Jie, Shen, Yang, Liu, Xiaoheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779398/
https://www.ncbi.nlm.nih.gov/pubmed/36555344
http://dx.doi.org/10.3390/ijms232415702
_version_ 1784856599865589760
author Pei, Tong
Su, Guanyue
Yang, Jie
Gao, Wenbo
Yang, Xinrui
Zhang, Yaojia
Ren, Jie
Shen, Yang
Liu, Xiaoheng
author_facet Pei, Tong
Su, Guanyue
Yang, Jie
Gao, Wenbo
Yang, Xinrui
Zhang, Yaojia
Ren, Jie
Shen, Yang
Liu, Xiaoheng
author_sort Pei, Tong
collection PubMed
description 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/cm(2) intensities) and treatment durations (10 dyn/cm(2) FSS with 0, 0.5, 1, 2 and 4 h treatment). The results demonstrate that the 1 h of 10 dyn/cm(2) 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.
format Online
Article
Text
id pubmed-9779398
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-97793982022-12-23 Fluid Shear Stress Regulates Osteogenic Differentiation via AnnexinA6-Mediated Autophagy in MC3T3-E1 Cells Pei, Tong Su, Guanyue Yang, Jie Gao, Wenbo Yang, Xinrui Zhang, Yaojia Ren, Jie Shen, Yang Liu, Xiaoheng Int J Mol Sci Article 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/cm(2) intensities) and treatment durations (10 dyn/cm(2) FSS with 0, 0.5, 1, 2 and 4 h treatment). The results demonstrate that the 1 h of 10 dyn/cm(2) 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. MDPI 2022-12-11 /pmc/articles/PMC9779398/ /pubmed/36555344 http://dx.doi.org/10.3390/ijms232415702 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pei, Tong
Su, Guanyue
Yang, Jie
Gao, Wenbo
Yang, Xinrui
Zhang, Yaojia
Ren, Jie
Shen, Yang
Liu, Xiaoheng
Fluid Shear Stress Regulates Osteogenic Differentiation via AnnexinA6-Mediated Autophagy in MC3T3-E1 Cells
title Fluid Shear Stress Regulates Osteogenic Differentiation via AnnexinA6-Mediated Autophagy in MC3T3-E1 Cells
title_full Fluid Shear Stress Regulates Osteogenic Differentiation via AnnexinA6-Mediated Autophagy in MC3T3-E1 Cells
title_fullStr Fluid Shear Stress Regulates Osteogenic Differentiation via AnnexinA6-Mediated Autophagy in MC3T3-E1 Cells
title_full_unstemmed Fluid Shear Stress Regulates Osteogenic Differentiation via AnnexinA6-Mediated Autophagy in MC3T3-E1 Cells
title_short Fluid Shear Stress Regulates Osteogenic Differentiation via AnnexinA6-Mediated Autophagy in MC3T3-E1 Cells
title_sort fluid shear stress regulates osteogenic differentiation via annexina6-mediated autophagy in mc3t3-e1 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779398/
https://www.ncbi.nlm.nih.gov/pubmed/36555344
http://dx.doi.org/10.3390/ijms232415702
work_keys_str_mv AT peitong fluidshearstressregulatesosteogenicdifferentiationviaannexina6mediatedautophagyinmc3t3e1cells
AT suguanyue fluidshearstressregulatesosteogenicdifferentiationviaannexina6mediatedautophagyinmc3t3e1cells
AT yangjie fluidshearstressregulatesosteogenicdifferentiationviaannexina6mediatedautophagyinmc3t3e1cells
AT gaowenbo fluidshearstressregulatesosteogenicdifferentiationviaannexina6mediatedautophagyinmc3t3e1cells
AT yangxinrui fluidshearstressregulatesosteogenicdifferentiationviaannexina6mediatedautophagyinmc3t3e1cells
AT zhangyaojia fluidshearstressregulatesosteogenicdifferentiationviaannexina6mediatedautophagyinmc3t3e1cells
AT renjie fluidshearstressregulatesosteogenicdifferentiationviaannexina6mediatedautophagyinmc3t3e1cells
AT shenyang fluidshearstressregulatesosteogenicdifferentiationviaannexina6mediatedautophagyinmc3t3e1cells
AT liuxiaoheng fluidshearstressregulatesosteogenicdifferentiationviaannexina6mediatedautophagyinmc3t3e1cells