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Microtubule stabilization targeting regenerative chondrocyte cluster for cartilage regeneration

Purpose: Chondrocytes (CHs) in cartilage undergo several detrimental events during the development of osteoarthritis (OA). However, the mechanism underlying CHs regeneration involved in pathogenesis is largely unknown. The aim of this study was to explore the underlying mechanism of regeneration of...

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Autores principales: Li, Jiawei, Fan, Chunmei, Lv, Zhongyang, Sun, Ziying, Han, Jie, Wang, Maochun, Jiang, Huiming, Sun, Kuoyang, Tan, Guihua, Guo, Hu, Liu, Anlong, Sun, Heng, Xu, Xingquan, Wu, Rui, Yan, Wenjin, Jiang, Qing, Ikegawa, Shiro, Chen, Xiao, Shi, Dongquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10283062/
https://www.ncbi.nlm.nih.gov/pubmed/37351173
http://dx.doi.org/10.7150/thno.85077
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author Li, Jiawei
Fan, Chunmei
Lv, Zhongyang
Sun, Ziying
Han, Jie
Wang, Maochun
Jiang, Huiming
Sun, Kuoyang
Tan, Guihua
Guo, Hu
Liu, Anlong
Sun, Heng
Xu, Xingquan
Wu, Rui
Yan, Wenjin
Jiang, Qing
Ikegawa, Shiro
Chen, Xiao
Shi, Dongquan
author_facet Li, Jiawei
Fan, Chunmei
Lv, Zhongyang
Sun, Ziying
Han, Jie
Wang, Maochun
Jiang, Huiming
Sun, Kuoyang
Tan, Guihua
Guo, Hu
Liu, Anlong
Sun, Heng
Xu, Xingquan
Wu, Rui
Yan, Wenjin
Jiang, Qing
Ikegawa, Shiro
Chen, Xiao
Shi, Dongquan
author_sort Li, Jiawei
collection PubMed
description Purpose: Chondrocytes (CHs) in cartilage undergo several detrimental events during the development of osteoarthritis (OA). However, the mechanism underlying CHs regeneration involved in pathogenesis is largely unknown. The aim of this study was to explore the underlying mechanism of regeneration of CHs involved in the pathological condition and the potential therapeutic strategies of cartilage repair. Methods and Materials: CHs were isolated from human cartilage in different OA stages and the high-resolution cellular architecture of human osteoarthritis was examined by applying single-cell RNA sequencing. The analysis of gene differential expression and gene set enrichment was utilized to reveal the relationship of cartilage regeneration and microtubule stabilization. Microtubule destabilizer (nocodazole) and microtubule stabilizer (docetaxel) treated-human primary CHs and rats cartilage defect model were used to investing the effects and downstream signaling pathway of microtubule stabilization on cartilage regeneration. Results: CHs subpopulations were identified on the basis of their gene markers and the data indicated an imbalance caused by an increase in the degeneration and disruption of CHs regeneration in OA samples. Interestingly, the CHs subpopulation namely CHI3L1(+) CHs, was characterized by the cell regenerative capacity, stem cell potency and the activated microtubule (MT) process. Furthermore, the data indicated that MT stabilization was effective in promoting cartilage regeneration in rats with cartilage injury model by inhibiting YAP activity. Conclusion: These findings lead to a new understanding of CHs regeneration in the OA pathophysiology context and suggest that MT stabilization is a promising therapeutic target for OA and cartilage injury.
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spelling pubmed-102830622023-06-22 Microtubule stabilization targeting regenerative chondrocyte cluster for cartilage regeneration Li, Jiawei Fan, Chunmei Lv, Zhongyang Sun, Ziying Han, Jie Wang, Maochun Jiang, Huiming Sun, Kuoyang Tan, Guihua Guo, Hu Liu, Anlong Sun, Heng Xu, Xingquan Wu, Rui Yan, Wenjin Jiang, Qing Ikegawa, Shiro Chen, Xiao Shi, Dongquan Theranostics Research Paper Purpose: Chondrocytes (CHs) in cartilage undergo several detrimental events during the development of osteoarthritis (OA). However, the mechanism underlying CHs regeneration involved in pathogenesis is largely unknown. The aim of this study was to explore the underlying mechanism of regeneration of CHs involved in the pathological condition and the potential therapeutic strategies of cartilage repair. Methods and Materials: CHs were isolated from human cartilage in different OA stages and the high-resolution cellular architecture of human osteoarthritis was examined by applying single-cell RNA sequencing. The analysis of gene differential expression and gene set enrichment was utilized to reveal the relationship of cartilage regeneration and microtubule stabilization. Microtubule destabilizer (nocodazole) and microtubule stabilizer (docetaxel) treated-human primary CHs and rats cartilage defect model were used to investing the effects and downstream signaling pathway of microtubule stabilization on cartilage regeneration. Results: CHs subpopulations were identified on the basis of their gene markers and the data indicated an imbalance caused by an increase in the degeneration and disruption of CHs regeneration in OA samples. Interestingly, the CHs subpopulation namely CHI3L1(+) CHs, was characterized by the cell regenerative capacity, stem cell potency and the activated microtubule (MT) process. Furthermore, the data indicated that MT stabilization was effective in promoting cartilage regeneration in rats with cartilage injury model by inhibiting YAP activity. Conclusion: These findings lead to a new understanding of CHs regeneration in the OA pathophysiology context and suggest that MT stabilization is a promising therapeutic target for OA and cartilage injury. Ivyspring International Publisher 2023-06-12 /pmc/articles/PMC10283062/ /pubmed/37351173 http://dx.doi.org/10.7150/thno.85077 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Li, Jiawei
Fan, Chunmei
Lv, Zhongyang
Sun, Ziying
Han, Jie
Wang, Maochun
Jiang, Huiming
Sun, Kuoyang
Tan, Guihua
Guo, Hu
Liu, Anlong
Sun, Heng
Xu, Xingquan
Wu, Rui
Yan, Wenjin
Jiang, Qing
Ikegawa, Shiro
Chen, Xiao
Shi, Dongquan
Microtubule stabilization targeting regenerative chondrocyte cluster for cartilage regeneration
title Microtubule stabilization targeting regenerative chondrocyte cluster for cartilage regeneration
title_full Microtubule stabilization targeting regenerative chondrocyte cluster for cartilage regeneration
title_fullStr Microtubule stabilization targeting regenerative chondrocyte cluster for cartilage regeneration
title_full_unstemmed Microtubule stabilization targeting regenerative chondrocyte cluster for cartilage regeneration
title_short Microtubule stabilization targeting regenerative chondrocyte cluster for cartilage regeneration
title_sort microtubule stabilization targeting regenerative chondrocyte cluster for cartilage regeneration
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10283062/
https://www.ncbi.nlm.nih.gov/pubmed/37351173
http://dx.doi.org/10.7150/thno.85077
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