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Theranostics 2023; 13(10):3480-3496. doi:10.7150/thno.85077 This issue Cite

Research Paper

Microtubule stabilization targeting regenerative chondrocyte cluster for cartilage regeneration

Jiawei Li1,3*, Chunmei Fan2,4,5,8,9*, Zhongyang Lv1*, Ziying Sun1, Jie Han2,5,8,9, Maochun Wang1, Huiming Jiang6, Kuoyang Sun1, Guihua Tan1, Hu Guo1, Anlong Liu1, Heng Sun1, Xingquan Xu1, Rui Wu1, Wenjin Yan1, Qing Jiang1, Shiro Ikegawa1,7, Xiao Chen2,4,8,9✉, Dongquan Shi1,9✉

1. State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, PR China.
2. Dr. Li Dak Sum-Yip Yio Chin Center for Stem Cells and Regenerative Medicine and Department of Orthopedic Surgery of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang, PR China.
3. Department of Orthopedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325200, Zhejiang, PR China.
4. Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, Department of Clinical Medicine, School of Medicine, Hangzhou City University, Hangzhou, 310000, Zhejiang, PR China.
5. Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang, PR China.
6. Department of Sports Medicine and Adult Reconstructive Surgery, the Affiliated Nanjing Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu, PR China.
7. Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Science (IMS, RIKEN), Tokyo 108-8639, Japan.
8. Department of Sports Medicine, Zhejiang University School of Medicine, Hangzhou, PR China.
9. China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou 310000, Zhejiang, PR China.
* Jiawei Li, Chunmei Fan and Zhongyang Lv contributed equally to this study.

✉ Corresponding authors: Dongquan Shi, State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, 321 Zhongshan Road, Nanjin More

Citation:
Li J, Fan C, Lv Z, Sun Z, Han J, Wang M, Jiang H, Sun K, Tan G, Guo H, Liu A, Sun H, Xu X, Wu R, Yan W, Jiang Q, Ikegawa S, Chen X, Shi D. Microtubule stabilization targeting regenerative chondrocyte cluster for cartilage regeneration. Theranostics 2023; 13(10):3480-3496. doi:10.7150/thno.85077. https://www.thno.org/v13p3480.htm
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Abstract

Graphic abstract

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.

Keywords: Cartilage regeneration, Chondrocytes, Microtubule stabilization, Single cell RNA sequencing, Yes associated protein

Citation styles

APA
Li, J., Fan, C., Lv, Z., Sun, Z., Han, J., Wang, M., Jiang, H., Sun, K., Tan, G., Guo, H., Liu, A., Sun, H., Xu, X., Wu, R., Yan, W., Jiang, Q., Ikegawa, S., Chen, X., Shi, D. (2023). Microtubule stabilization targeting regenerative chondrocyte cluster for cartilage regeneration. Theranostics, 13(10), 3480-3496. https://doi.org/10.7150/thno.85077.

ACS
Li, J.; Fan, C.; Lv, Z.; Sun, Z.; Han, J.; Wang, M.; Jiang, H.; Sun, K.; Tan, G.; Guo, H.; Liu, A.; Sun, H.; Xu, X.; Wu, R.; Yan, W.; Jiang, Q.; Ikegawa, S.; Chen, X.; Shi, D. Microtubule stabilization targeting regenerative chondrocyte cluster for cartilage regeneration. Theranostics 2023, 13 (10), 3480-3496. DOI: 10.7150/thno.85077.

NLM
Li J, Fan C, Lv Z, Sun Z, Han J, Wang M, Jiang H, Sun K, Tan G, Guo H, Liu A, Sun H, Xu X, Wu R, Yan W, Jiang Q, Ikegawa S, Chen X, Shi D. Microtubule stabilization targeting regenerative chondrocyte cluster for cartilage regeneration. Theranostics 2023; 13(10):3480-3496. doi:10.7150/thno.85077. https://www.thno.org/v13p3480.htm

CSE
Li J, Fan C, Lv Z, Sun Z, Han J, Wang M, Jiang H, Sun K, Tan G, Guo H, Liu A, Sun H, Xu X, Wu R, Yan W, Jiang Q, Ikegawa S, Chen X, Shi D. 2023. Microtubule stabilization targeting regenerative chondrocyte cluster for cartilage regeneration. Theranostics. 13(10):3480-3496.

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