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Instability and excessive mechanical loading mediate subchondral bone changes to induce osteoarthritis
BACKGROUND: To assess the diversified effects of mechanical instability, excessive mechanical loading on subchondral bone remodeling. And to investigate the underlying cartilage degeneration and osteoarthritis (OA) progression in ipsilateral and contralateral knees, given that OA progression always...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186756/ https://www.ncbi.nlm.nih.gov/pubmed/32355794 http://dx.doi.org/10.21037/atm.2020.02.103 |
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author | Zhu, Jianxi Zhu, Yong Xiao, Wenfeng Hu, Yihe Li, Yusheng |
author_facet | Zhu, Jianxi Zhu, Yong Xiao, Wenfeng Hu, Yihe Li, Yusheng |
author_sort | Zhu, Jianxi |
collection | PubMed |
description | BACKGROUND: To assess the diversified effects of mechanical instability, excessive mechanical loading on subchondral bone remodeling. And to investigate the underlying cartilage degeneration and osteoarthritis (OA) progression in ipsilateral and contralateral knees, given that OA progression always affects joints bilaterally. METHODS: Anterior cruciate ligament transection (ACLT) of the left knee was used to induce OA in C57/B6 mice for 1, 3 and 6 months. Both left (ipsilateral) and right (contralateral) knees underwent micro-computerized tomography (micro-CT) scan and morphological analysis. The subchondral bone metabolism analysis by immunostaining of tartrate-resistant acid phosphatase (TRAP) and Osterix. Behavioral analyses including von Frey test and CatWalk gait analysis were also performed. Western blot analysis was performed to assess the signaling pathways involved in OA progression. RESULTS: Analyses showed that various changes in ipsilateral and contralateral knees lead to OA progression. Articular cartilage was rapidly destroyed on the ipsilateral side but was only gradually destroyed on the contralateral side. Micro-CT data showed a rapid decrease with a subsequent partial recovery of bone volume in the late stage on the ipsilateral side, while a gradual condensation of bone density was seen on the contralateral side. Immunostaining showed increased osteoclastic and osteoblastic activity in the early stage on the ipsilateral side, but only slight osteoblastic changes on the contralateral side. Behavioral analyses including von Frey and gait analysis showed that contralateral knees compensate ipsilateral mechanical loading, but also that this mechanism failed to work in the late stage. CONCLUSIONS: Diversified mechanical loading properties lead to OA progression through different mechanisms of subchondral bone remodeling. Acute ACLT led to OA through bone density reduction, while the contralateral side developed OA gradually due to subchondral bone sclerosis. |
format | Online Article Text |
id | pubmed-7186756 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-71867562020-04-30 Instability and excessive mechanical loading mediate subchondral bone changes to induce osteoarthritis Zhu, Jianxi Zhu, Yong Xiao, Wenfeng Hu, Yihe Li, Yusheng Ann Transl Med Original Article BACKGROUND: To assess the diversified effects of mechanical instability, excessive mechanical loading on subchondral bone remodeling. And to investigate the underlying cartilage degeneration and osteoarthritis (OA) progression in ipsilateral and contralateral knees, given that OA progression always affects joints bilaterally. METHODS: Anterior cruciate ligament transection (ACLT) of the left knee was used to induce OA in C57/B6 mice for 1, 3 and 6 months. Both left (ipsilateral) and right (contralateral) knees underwent micro-computerized tomography (micro-CT) scan and morphological analysis. The subchondral bone metabolism analysis by immunostaining of tartrate-resistant acid phosphatase (TRAP) and Osterix. Behavioral analyses including von Frey test and CatWalk gait analysis were also performed. Western blot analysis was performed to assess the signaling pathways involved in OA progression. RESULTS: Analyses showed that various changes in ipsilateral and contralateral knees lead to OA progression. Articular cartilage was rapidly destroyed on the ipsilateral side but was only gradually destroyed on the contralateral side. Micro-CT data showed a rapid decrease with a subsequent partial recovery of bone volume in the late stage on the ipsilateral side, while a gradual condensation of bone density was seen on the contralateral side. Immunostaining showed increased osteoclastic and osteoblastic activity in the early stage on the ipsilateral side, but only slight osteoblastic changes on the contralateral side. Behavioral analyses including von Frey and gait analysis showed that contralateral knees compensate ipsilateral mechanical loading, but also that this mechanism failed to work in the late stage. CONCLUSIONS: Diversified mechanical loading properties lead to OA progression through different mechanisms of subchondral bone remodeling. Acute ACLT led to OA through bone density reduction, while the contralateral side developed OA gradually due to subchondral bone sclerosis. AME Publishing Company 2020-03 /pmc/articles/PMC7186756/ /pubmed/32355794 http://dx.doi.org/10.21037/atm.2020.02.103 Text en 2020 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Zhu, Jianxi Zhu, Yong Xiao, Wenfeng Hu, Yihe Li, Yusheng Instability and excessive mechanical loading mediate subchondral bone changes to induce osteoarthritis |
title | Instability and excessive mechanical loading mediate subchondral bone changes to induce osteoarthritis |
title_full | Instability and excessive mechanical loading mediate subchondral bone changes to induce osteoarthritis |
title_fullStr | Instability and excessive mechanical loading mediate subchondral bone changes to induce osteoarthritis |
title_full_unstemmed | Instability and excessive mechanical loading mediate subchondral bone changes to induce osteoarthritis |
title_short | Instability and excessive mechanical loading mediate subchondral bone changes to induce osteoarthritis |
title_sort | instability and excessive mechanical loading mediate subchondral bone changes to induce osteoarthritis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186756/ https://www.ncbi.nlm.nih.gov/pubmed/32355794 http://dx.doi.org/10.21037/atm.2020.02.103 |
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