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Excessive mechanical stretch-mediated osteoblasts promote the catabolism and apoptosis of chondrocytes via the Wnt/β-catenin signaling pathway
Excessive biomechanical loading is considered an important cause of osteoarthritis. Although the mechanical responses of chondrocytes and osteoblasts have been investigated, their communication during mechanical loading and the underlying molecular mechanisms are not yet fully known. The present stu...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222797/ https://www.ncbi.nlm.nih.gov/pubmed/34165157 http://dx.doi.org/10.3892/mmr.2021.12232 |
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author | Song, Cheng-Xian Liu, Sheng-Yao Zhu, Wen-Ting Xu, Shao-Yong Ni, Guo-Xin |
author_facet | Song, Cheng-Xian Liu, Sheng-Yao Zhu, Wen-Ting Xu, Shao-Yong Ni, Guo-Xin |
author_sort | Song, Cheng-Xian |
collection | PubMed |
description | Excessive biomechanical loading is considered an important cause of osteoarthritis. Although the mechanical responses of chondrocytes and osteoblasts have been investigated, their communication during mechanical loading and the underlying molecular mechanisms are not yet fully known. The present study investigated the effects of excessive mechanically stretched osteoblasts on the metabolism and apoptosis of chondrocytes, and also assessed the involvement of the Wnt/β-catenin signaling pathway. In the present study, rat chondrocytes and osteoblasts were subjected to mechanical tensile strain, and an indirect chondrocyte-osteoblast co-culture model was established. Reverse transcription-quantitative PCR and western blotting were performed to determine the expression levels of genes and proteins of interest. An ELISA was performed to investigate the levels of cytokines, including matrix metalloproteinase (MMP) 13, MMP 3, interleukin-6 (IL-6) and prostaglandin E2 (PG E2), released from osteoblasts. Flow cytometry was performed to detect the apoptosis of chondrocytes exposed to stretched osteoblast conditioned culture medium. The levels of MMP 13, IL-6 and PG E2 increased significantly in the supernatants of stretched osteoblasts compared with the un-stretched group. By contrast, the mRNA expression levels of Collagen 1a and alkaline phosphatase were significantly decreased in osteoblasts subjected to mechanical stretch compared with the un-stretched group. The mRNA expression level of Collagen 2a was significantly decreased, whereas the expression levels of MMP 13 and a disintegrin and metalloproteinase with thrombospondin-like motifs 5 were significantly increased in chondrocytes subjected to mechanical stretch compared with the un-stretched group. In the co-culture model, the results indicated that excessive mechanically stretched osteoblasts induced the catabolism and apoptosis of chondrocytes, which was partly inhibited by Wnt inhibitor XAV-939. The results of the present study demonstrated that excessive mechanical stretch led to chondrocyte degradation and inhibited osteoblast osteogenic differentiation; furthermore, excessive mechanically stretched osteoblasts induced the catabolism and apoptosis of chondrocytes via the Wnt/β-catenin signaling pathway. |
format | Online Article Text |
id | pubmed-8222797 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-82227972021-06-26 Excessive mechanical stretch-mediated osteoblasts promote the catabolism and apoptosis of chondrocytes via the Wnt/β-catenin signaling pathway Song, Cheng-Xian Liu, Sheng-Yao Zhu, Wen-Ting Xu, Shao-Yong Ni, Guo-Xin Mol Med Rep Articles Excessive biomechanical loading is considered an important cause of osteoarthritis. Although the mechanical responses of chondrocytes and osteoblasts have been investigated, their communication during mechanical loading and the underlying molecular mechanisms are not yet fully known. The present study investigated the effects of excessive mechanically stretched osteoblasts on the metabolism and apoptosis of chondrocytes, and also assessed the involvement of the Wnt/β-catenin signaling pathway. In the present study, rat chondrocytes and osteoblasts were subjected to mechanical tensile strain, and an indirect chondrocyte-osteoblast co-culture model was established. Reverse transcription-quantitative PCR and western blotting were performed to determine the expression levels of genes and proteins of interest. An ELISA was performed to investigate the levels of cytokines, including matrix metalloproteinase (MMP) 13, MMP 3, interleukin-6 (IL-6) and prostaglandin E2 (PG E2), released from osteoblasts. Flow cytometry was performed to detect the apoptosis of chondrocytes exposed to stretched osteoblast conditioned culture medium. The levels of MMP 13, IL-6 and PG E2 increased significantly in the supernatants of stretched osteoblasts compared with the un-stretched group. By contrast, the mRNA expression levels of Collagen 1a and alkaline phosphatase were significantly decreased in osteoblasts subjected to mechanical stretch compared with the un-stretched group. The mRNA expression level of Collagen 2a was significantly decreased, whereas the expression levels of MMP 13 and a disintegrin and metalloproteinase with thrombospondin-like motifs 5 were significantly increased in chondrocytes subjected to mechanical stretch compared with the un-stretched group. In the co-culture model, the results indicated that excessive mechanically stretched osteoblasts induced the catabolism and apoptosis of chondrocytes, which was partly inhibited by Wnt inhibitor XAV-939. The results of the present study demonstrated that excessive mechanical stretch led to chondrocyte degradation and inhibited osteoblast osteogenic differentiation; furthermore, excessive mechanically stretched osteoblasts induced the catabolism and apoptosis of chondrocytes via the Wnt/β-catenin signaling pathway. D.A. Spandidos 2021-08 2021-06-17 /pmc/articles/PMC8222797/ /pubmed/34165157 http://dx.doi.org/10.3892/mmr.2021.12232 Text en Copyright: © Song et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Song, Cheng-Xian Liu, Sheng-Yao Zhu, Wen-Ting Xu, Shao-Yong Ni, Guo-Xin Excessive mechanical stretch-mediated osteoblasts promote the catabolism and apoptosis of chondrocytes via the Wnt/β-catenin signaling pathway |
title | Excessive mechanical stretch-mediated osteoblasts promote the catabolism and apoptosis of chondrocytes via the Wnt/β-catenin signaling pathway |
title_full | Excessive mechanical stretch-mediated osteoblasts promote the catabolism and apoptosis of chondrocytes via the Wnt/β-catenin signaling pathway |
title_fullStr | Excessive mechanical stretch-mediated osteoblasts promote the catabolism and apoptosis of chondrocytes via the Wnt/β-catenin signaling pathway |
title_full_unstemmed | Excessive mechanical stretch-mediated osteoblasts promote the catabolism and apoptosis of chondrocytes via the Wnt/β-catenin signaling pathway |
title_short | Excessive mechanical stretch-mediated osteoblasts promote the catabolism and apoptosis of chondrocytes via the Wnt/β-catenin signaling pathway |
title_sort | excessive mechanical stretch-mediated osteoblasts promote the catabolism and apoptosis of chondrocytes via the wnt/β-catenin signaling pathway |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222797/ https://www.ncbi.nlm.nih.gov/pubmed/34165157 http://dx.doi.org/10.3892/mmr.2021.12232 |
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