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Sox9 Potentiates BMP2-Induced Chondrogenic Differentiation and Inhibits BMP2-Induced Osteogenic Differentiation

  • Junyi Liao
  • Ning Hu
  • Nian Zhou
  • Chen Zhao
  • Xi Liang
  • Hong Chen
  • Wei Xu
  • Cheng Chen
  • Qiang Cheng
  • Wei HuangEmail author
Chapter

Abstract

Bone morphogenetic protein 2 (BMP2) is one of the key chondrogenic growth factors involved in the cartilage regeneration. However, it also exhibits osteogenic abilities and triggers endochondral ossification. Effective chondrogenesis and inhibition of BMP2-induced osteogenesis and endochondral ossification can be achieved by directing the mesenchymal stem cells (MSCs) towards chondrocyte lineage with chondrogenic factors, such as Sox9. Here we investigated the effects of Sox9 on BMP2-induced chondrogenic and osteogenic differentiation of MSCs. We found that exogenous overexpression of Sox9 enhanced the BMP2-induced chondrogenic differentiation of MSCs in vitro. Also, it inhibited early and late osteogenic differentiation of MSCs in vitro. Subcutaneous stem cell implantation demonstrated Sox9-potentiated BMP2-induced cartilage formation and inhibited endochondral ossification. Mouse limb cultures indicated that BMP2 and Sox9 acted synergistically to stimulate chondrocyte proliferation, and Sox9 inhibited BMP2-induced chondrocyte hypertrophy and ossification. This study strongly suggests that Sox9 potentiates BMP2-induced MSC chondrogenic differentiation and cartilage formation, and inhibits BMP2-induced MSC osteogenic differentiation and endochondral ossification. Thus, exogenous overexpression of Sox9 in BMP2-induced mesenchymal stem cell differentiation may be a new strategy for cartilage tissue engineering.

Keywords

Sox9 Bmp2 Chondogenic growth factors MSC 

Notes

Acknowledgments

We are grateful for the Department of Clinical Hematology, Third Military Medical University, and all persons in this department. We greatly thank Pro. Tong-Chuan He (Molecular Oncology Laboratory, Department of Surgery, University of Chicago Medical Center) for the use of AdBMP2, AdSox9, and AdGFP.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Junyi Liao
    • 1
  • Ning Hu
    • 1
  • Nian Zhou
    • 1
  • Chen Zhao
    • 1
  • Xi Liang
    • 1
  • Hong Chen
    • 1
  • Wei Xu
    • 1
  • Cheng Chen
    • 1
  • Qiang Cheng
    • 1
  • Wei Huang
    • 1
    Email author
  1. 1.Department of Orthopaedic SurgeryThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

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