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Up‐regulation of TβRIII facilitates the osteogenesis of supraspinous ligament‐derived fibroblasts from patients with ankylosing spondylitis
Spinal supraspinous ligament (SL) osteogenesis is the key risk of ankylosing spondylitis (AS), with an unclear pathogenesis. We previously found that transforming growth factor β1 (TGF‐β1), bone morphogenetic proteins (eg BMP2) and type III TGF‐β1 receptor (TβRIII) expression were markedly up‐regula...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875912/ https://www.ncbi.nlm.nih.gov/pubmed/33410269 http://dx.doi.org/10.1111/jcmm.16262 |
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author | Zhang, Ying Chen, Wu‐gui Yang, Si‐zhen Qiu, Hao Hu, Xu Qiu, Yi‐yun Wen, Xuan Zhou, Yue Chu, Tong‐wei |
author_facet | Zhang, Ying Chen, Wu‐gui Yang, Si‐zhen Qiu, Hao Hu, Xu Qiu, Yi‐yun Wen, Xuan Zhou, Yue Chu, Tong‐wei |
author_sort | Zhang, Ying |
collection | PubMed |
description | Spinal supraspinous ligament (SL) osteogenesis is the key risk of ankylosing spondylitis (AS), with an unclear pathogenesis. We previously found that transforming growth factor β1 (TGF‐β1), bone morphogenetic proteins (eg BMP2) and type III TGF‐β1 receptor (TβRIII) expression were markedly up‐regulated in AS‐SLs. However, the roles of these closely related molecules in AS are unknown. Here, we showed that BMP2, TGF‐β1, TβRIII and S100A4 (a fibroblast marker) were abundant in active osteogenic AS‐SL tissues. In vitro, AS‐SL fibroblasts (AS‐SLFs) showed high BMP2, TGF‐β1 and TβRIII expression and auto‐osteogenic capacity. We further evaluated the role of TβRIII in the osteogenesis of normal SLFs. BMP2 combined with TGF‐β1 induced the osteogenesis of TβRIII‐overexpressing SLFs, but the activity was lost in SLFs upon TβRIII knockdown. Moreover, our data suggested that BMP2 combined with TGF‐β1 significantly activated both TGF‐β1/Smad signalling and BMP2/Smad/RUNX2 signalling to induce osteogenesis of SLFs with TβRIII up‐regulation. Furthermore, our multi‐strategy molecular interaction analysis approach indicated that TGF‐β1 presented BMP2 to TβRIII, sequentially facilitating BMP2 recognition by BMPR1A and promoting the osteogenesis of TβRIII‐overexpressing SLFs. Collectively, our results indicate that TGF‐β1 combined with BMP2 may participate in the osteogenic differentiation of AS‐SLF by acting on up‐regulated TβRIII, resulting in excessive activation of both TGF‐β1/Smad and BMP2/BMPR1A/Smad/RUNX2 signalling. |
format | Online Article Text |
id | pubmed-7875912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78759122021-02-18 Up‐regulation of TβRIII facilitates the osteogenesis of supraspinous ligament‐derived fibroblasts from patients with ankylosing spondylitis Zhang, Ying Chen, Wu‐gui Yang, Si‐zhen Qiu, Hao Hu, Xu Qiu, Yi‐yun Wen, Xuan Zhou, Yue Chu, Tong‐wei J Cell Mol Med Original Articles Spinal supraspinous ligament (SL) osteogenesis is the key risk of ankylosing spondylitis (AS), with an unclear pathogenesis. We previously found that transforming growth factor β1 (TGF‐β1), bone morphogenetic proteins (eg BMP2) and type III TGF‐β1 receptor (TβRIII) expression were markedly up‐regulated in AS‐SLs. However, the roles of these closely related molecules in AS are unknown. Here, we showed that BMP2, TGF‐β1, TβRIII and S100A4 (a fibroblast marker) were abundant in active osteogenic AS‐SL tissues. In vitro, AS‐SL fibroblasts (AS‐SLFs) showed high BMP2, TGF‐β1 and TβRIII expression and auto‐osteogenic capacity. We further evaluated the role of TβRIII in the osteogenesis of normal SLFs. BMP2 combined with TGF‐β1 induced the osteogenesis of TβRIII‐overexpressing SLFs, but the activity was lost in SLFs upon TβRIII knockdown. Moreover, our data suggested that BMP2 combined with TGF‐β1 significantly activated both TGF‐β1/Smad signalling and BMP2/Smad/RUNX2 signalling to induce osteogenesis of SLFs with TβRIII up‐regulation. Furthermore, our multi‐strategy molecular interaction analysis approach indicated that TGF‐β1 presented BMP2 to TβRIII, sequentially facilitating BMP2 recognition by BMPR1A and promoting the osteogenesis of TβRIII‐overexpressing SLFs. Collectively, our results indicate that TGF‐β1 combined with BMP2 may participate in the osteogenic differentiation of AS‐SLF by acting on up‐regulated TβRIII, resulting in excessive activation of both TGF‐β1/Smad and BMP2/BMPR1A/Smad/RUNX2 signalling. John Wiley and Sons Inc. 2021-01-06 2021-02 /pmc/articles/PMC7875912/ /pubmed/33410269 http://dx.doi.org/10.1111/jcmm.16262 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Zhang, Ying Chen, Wu‐gui Yang, Si‐zhen Qiu, Hao Hu, Xu Qiu, Yi‐yun Wen, Xuan Zhou, Yue Chu, Tong‐wei Up‐regulation of TβRIII facilitates the osteogenesis of supraspinous ligament‐derived fibroblasts from patients with ankylosing spondylitis |
title | Up‐regulation of TβRIII facilitates the osteogenesis of supraspinous ligament‐derived fibroblasts from patients with ankylosing spondylitis |
title_full | Up‐regulation of TβRIII facilitates the osteogenesis of supraspinous ligament‐derived fibroblasts from patients with ankylosing spondylitis |
title_fullStr | Up‐regulation of TβRIII facilitates the osteogenesis of supraspinous ligament‐derived fibroblasts from patients with ankylosing spondylitis |
title_full_unstemmed | Up‐regulation of TβRIII facilitates the osteogenesis of supraspinous ligament‐derived fibroblasts from patients with ankylosing spondylitis |
title_short | Up‐regulation of TβRIII facilitates the osteogenesis of supraspinous ligament‐derived fibroblasts from patients with ankylosing spondylitis |
title_sort | up‐regulation of tβriii facilitates the osteogenesis of supraspinous ligament‐derived fibroblasts from patients with ankylosing spondylitis |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875912/ https://www.ncbi.nlm.nih.gov/pubmed/33410269 http://dx.doi.org/10.1111/jcmm.16262 |
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