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Mechanical Loading Promotes the Migration of Endogenous Stem Cells and Chondrogenic Differentiation in a Mouse Model of Osteoarthritis

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Abstract

Osteoarthritis (OA) is a major health problem, characterized by progressive cartilage degeneration. Previous works have shown that mechanical loading can alleviate OA symptoms by suppressing catabolic activities. This study evaluated whether mechanical loading can enhance anabolic activities by facilitating the recruitment of stem cells for chondrogenesis. We evaluated cartilage degradation in a mouse model of OA through histology with H&E and safranin O staining. We also evaluated the migration and chondrogenic ability of stem cells using in vitro assays, including immunohistochemistry, immunofluorescence, and Western blot analysis. The result showed that the OA mice that received mechanical loading exhibited resilience to cartilage damage. Compared to the OA group, mechanical loading promoted the expression of Piezo1 and the migration of stem cells was promoted via the SDF-1/CXCR4 axis. Also, the chondrogenic differentiation was enhanced by the upregulation of SOX9, a transcription factor important for chondrogenesis. Collectively, the results revealed that mechanical loading facilitated cartilage repair by promoting the migration and chondrogenic differentiation of endogenous stem cells. This study provided new insights into the loading-driven engagement of endogenous stem cells and the enhancement of anabolic responses for the treatment of OA.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81772405 and 81572100 to P. Zhang; 81601863 to X. Li).

Funding

National Natural Science Foundation of China,81772405,Ping Zhang,81572100,Ping Zhang,81601863,Xinle Li

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Authors and Affiliations

  1. Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin, 300070, China

    Jie Li, Xiaoyu Wang, Xinle Li, Daquan Liu, Lidong Zhai, Ran Kang & Ping Zhang

  2. Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, 300070, China

    Jie Li, Xinle Li, Daquan Liu & Ping Zhang

  3. Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China

    Xuetong Wang

  4. Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202, USA

    Hiroki Yokota

  5. Center for Health Sciences and Engineering, Hebei Key Laboratory of Biomaterials and Smart Theranostics, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin, 300131, China

    Lei Yang

  6. Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University, Tianjin, 300052, China

    Ping Zhang

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  1. Jie Li
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Contributions

PZ, JL, and XW designed research; XW, JL, RK and XL conducted research; DL, LZ, LY, RK and XW collected the data; JL, XW, XL, RK, LY, HY, and PZ analyzed the data; PZ JL, and XW wrote the manuscript; PZ approved the final manuscript as submitted; PZ accepted responsibility for the integrity of data analysis.

Corresponding author

Correspondence to Ping Zhang.

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Competing interest

Jie Li, Xiaoyu Wang, Xinle Li, Daquan Liu, Lidong Zhai, Xuetong Wang, Ran Kang, Hiroki Yokota, Lei Yang, Ping Zhang declare that they have no competing interests.

Resaerch Involving Human and Animal Rights

All experiments were carried out according to the National Institutes of Health Guide for Care and Use of Laboratory Animals and were approved by the Ethics Committee of Tianjin Medical University. No human studies were performed in the course of these experiments.

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Li, J., Wang, X., Li, X. et al. Mechanical Loading Promotes the Migration of Endogenous Stem Cells and Chondrogenic Differentiation in a Mouse Model of Osteoarthritis. Calcif Tissue Int 112, 363–376 (2023). https://doi.org/10.1007/s00223-022-01052-1

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