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Regulation of the integrin αVβ3- actin filaments axis in early osteogenesis of human fibroblasts under cyclic tensile stress

BACKGROUND: Integrins play a prominent role in osteogenic differentiation by transmitting both mechanical and chemical signals. Integrin expression is closely associated with tensile stress, which has a positive effect on osteogenic differentiation. We investigated the relationship between integrin...

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Autores principales: Peng, Yan, Qu, Rongmei, Feng, Yanting, Huang, Xiaolan, Yang, Yuchao, Fan, Tingyu, Sun, Bing, Khan, Asmat Ullah, Wu, Shutong, Dai, Jingxing, Ouyang, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496073/
https://www.ncbi.nlm.nih.gov/pubmed/34620239
http://dx.doi.org/10.1186/s13287-021-02597-y
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author Peng, Yan
Qu, Rongmei
Feng, Yanting
Huang, Xiaolan
Yang, Yuchao
Fan, Tingyu
Sun, Bing
Khan, Asmat Ullah
Wu, Shutong
Dai, Jingxing
Ouyang, Jun
author_facet Peng, Yan
Qu, Rongmei
Feng, Yanting
Huang, Xiaolan
Yang, Yuchao
Fan, Tingyu
Sun, Bing
Khan, Asmat Ullah
Wu, Shutong
Dai, Jingxing
Ouyang, Jun
author_sort Peng, Yan
collection PubMed
description BACKGROUND: Integrins play a prominent role in osteogenic differentiation by transmitting both mechanical and chemical signals. Integrin expression is closely associated with tensile stress, which has a positive effect on osteogenic differentiation. We investigated the relationship between integrin αVβ3 and tensile stress. METHODS: Human fibroblasts were treated with c (RGDyk) and lentivirus transduction to inhibit function of integrin αVβ3. Y-15, cytochalasin D and verteporfin were used to inhibit phosphorylation of FAK, polymerization of microfilament and function of nuclear YAP, respectively. Fibroblasts were exposed to a cyclic tensile stress of 10% at 0.5 Hz, once a day for 2 h each application. Fibroblasts were harvested on day 4 and 7 post-treatment. The expression of ALP, RUNX2, integrin αVβ3, β-actin, talin-1, FAK, vinculin, and nuclear YAP was detected by Western blot or qRT-PCR. The expression and distribution of integrin αVβ3, vinculin, microfilament and nuclear YAP. RESULTS: Cyclic tensile stress was found to promote expression of ALP and RUNX2. Inhibition of integrin αVβ3 activation downregulated the rearrangement of microfilament and the expression of ALP, RUNX2 and nuclear YAP. When the polymerization of microfilament was inhibited the expression of ALP, RUNX2 and nuclear YAP were decreased. The phosphorylation of FAK induced by cyclic tensile stress reduced by the inhibition of integrin αVβ3. The expression of ALP and RUNX2 was decreased by inhibition of phosphorylation of FAK and inhibition of nuclear YAP. CONCLUSIONS: Cyclic tensile stress promotes osteogenesis of human fibroblasts via integrin αVβ3-microfilament axis. Phosphorylation of FAK and nuclear YAP participates in this process. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02597-y.
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spelling pubmed-84960732021-10-07 Regulation of the integrin αVβ3- actin filaments axis in early osteogenesis of human fibroblasts under cyclic tensile stress Peng, Yan Qu, Rongmei Feng, Yanting Huang, Xiaolan Yang, Yuchao Fan, Tingyu Sun, Bing Khan, Asmat Ullah Wu, Shutong Dai, Jingxing Ouyang, Jun Stem Cell Res Ther Research BACKGROUND: Integrins play a prominent role in osteogenic differentiation by transmitting both mechanical and chemical signals. Integrin expression is closely associated with tensile stress, which has a positive effect on osteogenic differentiation. We investigated the relationship between integrin αVβ3 and tensile stress. METHODS: Human fibroblasts were treated with c (RGDyk) and lentivirus transduction to inhibit function of integrin αVβ3. Y-15, cytochalasin D and verteporfin were used to inhibit phosphorylation of FAK, polymerization of microfilament and function of nuclear YAP, respectively. Fibroblasts were exposed to a cyclic tensile stress of 10% at 0.5 Hz, once a day for 2 h each application. Fibroblasts were harvested on day 4 and 7 post-treatment. The expression of ALP, RUNX2, integrin αVβ3, β-actin, talin-1, FAK, vinculin, and nuclear YAP was detected by Western blot or qRT-PCR. The expression and distribution of integrin αVβ3, vinculin, microfilament and nuclear YAP. RESULTS: Cyclic tensile stress was found to promote expression of ALP and RUNX2. Inhibition of integrin αVβ3 activation downregulated the rearrangement of microfilament and the expression of ALP, RUNX2 and nuclear YAP. When the polymerization of microfilament was inhibited the expression of ALP, RUNX2 and nuclear YAP were decreased. The phosphorylation of FAK induced by cyclic tensile stress reduced by the inhibition of integrin αVβ3. The expression of ALP and RUNX2 was decreased by inhibition of phosphorylation of FAK and inhibition of nuclear YAP. CONCLUSIONS: Cyclic tensile stress promotes osteogenesis of human fibroblasts via integrin αVβ3-microfilament axis. Phosphorylation of FAK and nuclear YAP participates in this process. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02597-y. BioMed Central 2021-10-07 /pmc/articles/PMC8496073/ /pubmed/34620239 http://dx.doi.org/10.1186/s13287-021-02597-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Peng, Yan
Qu, Rongmei
Feng, Yanting
Huang, Xiaolan
Yang, Yuchao
Fan, Tingyu
Sun, Bing
Khan, Asmat Ullah
Wu, Shutong
Dai, Jingxing
Ouyang, Jun
Regulation of the integrin αVβ3- actin filaments axis in early osteogenesis of human fibroblasts under cyclic tensile stress
title Regulation of the integrin αVβ3- actin filaments axis in early osteogenesis of human fibroblasts under cyclic tensile stress
title_full Regulation of the integrin αVβ3- actin filaments axis in early osteogenesis of human fibroblasts under cyclic tensile stress
title_fullStr Regulation of the integrin αVβ3- actin filaments axis in early osteogenesis of human fibroblasts under cyclic tensile stress
title_full_unstemmed Regulation of the integrin αVβ3- actin filaments axis in early osteogenesis of human fibroblasts under cyclic tensile stress
title_short Regulation of the integrin αVβ3- actin filaments axis in early osteogenesis of human fibroblasts under cyclic tensile stress
title_sort regulation of the integrin αvβ3- actin filaments axis in early osteogenesis of human fibroblasts under cyclic tensile stress
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496073/
https://www.ncbi.nlm.nih.gov/pubmed/34620239
http://dx.doi.org/10.1186/s13287-021-02597-y
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