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

  • Liangliang Xu
  • E Shunmei
  • Sien Lin
  • Yonghui Hou
  • Weiping Lin
  • Wei He
  • Haibin WangEmail author
  • Gang LiEmail author
Regular Article

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.

Keywords

rMSCs Sox11 Cartilage Chondrocyte Chondrogenesis β-Catenin 

Notes

Author 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.

Funding information

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

441_2018_2979_MOESM1_ESM.docx (13 kb)
ESM 1 (DOCX 13 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Liangliang Xu
    • 1
    • 2
  • E Shunmei
    • 3
  • Sien Lin
    • 4
  • Yonghui Hou
    • 1
    • 4
  • Weiping Lin
    • 4
  • Wei He
    • 1
    • 2
  • Haibin Wang
    • 1
    • 2
    Email author
  • Gang Li
    • 4
    • 5
    Email author
  1. 1.Key Laboratory of Orthopaedics & Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, The First Clinical Medical CollegeGuangzhou University of Chinese MedicineGuangzhouPeople’s Republic of China
  2. 2.Laboratory of Orthopaedics & Traumatology, Lingnan Medical Research CenterGuangzhou University of Chinese MedicineGuangzhouPeople’s Republic of China
  3. 3.Department of Laboratory MedicineThe Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhouChina
  4. 4.Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Prince of Wales HospitalThe Chinese University of Hong KongHong Kong, SARPeople’s Republic of China
  5. 5.The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal SystemThe Chinese University of Hong Kong Shenzhen Research InstituteShenzhenPeople’s Republic of China

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