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Sox11-modified mesenchymal stem cells accelerate cartilage defect repair in SD rats

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Abstract

Cartilage has a limited capacity to heal. Previously, we have shown that overexpression of Sox11 in rMSCs (Rat Mesenchymal Stem Cells) by lentivirus-mediated gene transfer leads to enhanced tri-lineage differentiation and accelerated bone formation in fracture model of rats. We observed that the fracture repair in the rats that received Sox11-modified rMSCs injection proceeded through an endochondral ossification process much faster than those in the control groups. However, the detailed role of Sox11 in rMSCs chondrogenic differentiation, as well as cartilage defect, is still not clearly clarified. Therefore, this study tests the hypothesis that Sox11 promotes chondrogenesis and cartilage defect repair by regulating β-catenin. Sox11 was transduced into rMSCs using lentiviruses. The expression levels of β-catenin and its downstream genes were evaluated by quantitative RT-PCR. The transcriptional activation of β-catenin was proved by dual-luciferase reporter assay and co-immunoprecipitation was performed to evaluate Sox11-β-catenin interaction. In addition, a cartilage defect model in SD rats was used to evaluate the cartilage regeneration ability of Sox11-modified rMSCs in vivo. We found that Sox11 transcriptionally activated β-catenin expression and discovered the core promoter region (from − 242 to − 1414) of β-catenin gene for Sox11 binding. In addition, Sox11 might regulate β-catenin at the post-transcriptional level by protein-protein interaction. Finally, using a cartilage defect model in rats, we found Sox11-modified rMSCs could improve cartilage regeneration. Taken together, our study shows that Sox11 is an important regulator of chondrogenesis and Sox11-modified rMSCs may have clinical implication for accelerating cartilage defect healing.

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Funding

The work was partially supported by grants from the Hong Kong Government Research Grant Council, General Research Fund (14119115, 14160917, 14120118, 9054014 N_CityU102/15 and T13-402/17-N); National Natural Science Foundation of China (81430049, 81772322, 81772404); Hong Kong Innovation Technology Commission Funds (ITS/UIM-305); and grants from Guangdong provincial science and technology project (2017A050506046) and Shenzhen City Science and Technology Bureau (JCYJ20150630165236960). This study was also supported in part by SMART program, Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong and the research was made possible by resources donated by Lui Che Woo Foundation Limited.

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Author notes

  1. Liangliang Xu and E Shunmei contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Orthopaedics & Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China

    Liangliang Xu, Yonghui Hou, Wei He & Haibin Wang

  2. Laboratory of Orthopaedics & Traumatology, Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Jichang Road, Baiyun District, Guangzhou, People’s Republic of China

    Liangliang Xu, Wei He & Haibin Wang

  3. Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China

    E Shunmei

  4. Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, People’s Republic of China

    Sien Lin, Yonghui Hou, Weiping Lin & Gang Li

  5. The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, People’s Republic of China

    Gang Li

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  1. Liangliang Xu
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Contributions

Study design: Gang, Haibin; Acquisition of data: Liangliang, Shunmei, Sien, Yonghui; Analysis and interpretation of data: Liangliang, Shunmei, Sien, Yonghui; Manuscript preparation: Liangliang, Shunmei; Statistical analysis: Weiping, Wei.

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Correspondence to Haibin Wang or Gang Li.

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Xu, L., Shunmei, E., Lin, S. et al. Sox11-modified mesenchymal stem cells accelerate cartilage defect repair in SD rats. Cell Tissue Res 376, 247–255 (2019). https://doi.org/10.1007/s00441-018-02979-4

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