Cell and Tissue Research

, Volume 368, Issue 1, pp 93–104 | Cite as

Downregulation of CITED2 contributes to TGFβ-mediated senescence of tendon-derived stem cells

  • Chao Hu
  • Yan Zhang
  • Kanglai Tang
  • Yuchun LuoEmail author
  • Yunpeng Liu
  • Wan Chen
Regular Article


Tendon-derived stem cells (TDSCs) are multipotent adult stem cells with potential applications in tendon and tendon–bone junction repair. However, cellular characteristics change during in vitro passaging. Therefore, elucidation of the molecular and cellular mechanisms of tendon aging will be essential for the development of TDSC-based therapies. The aim of this study is to investigate the effect of CITED2, a nuclear regulator and transforming growth factor β2 (TGFβ2) on TDSC proliferation and senescence by comparing cells derived from Achilles tendon biopsies of young individuals (Y-TDSC) with those of older patients (O-TDSC). Our results showed that CITED2 mRNA and protein expression levels were significantly higher in Y-TDSCs than in O-TDSCs and O-TDSCs displayed decreased proliferation and increased senescence compared with Y-TDSCs. Furthermore, high levels of CITED2 protein expression in Y-TDSCs correlated with the downregulation of SP1 and p21 and the upregulation of MYC, potentially indicating the mechanism by which CITED2 upregulates TDSC proliferation. TGFβ2 was found to downregulate the expression of the CITED2 gene and knockdown of CITED2 abolished the effect of TGFβ2 on TDSC proliferation and senescence. Thus, the downregulation of CITED2 contributes to TGFβ-mediated senescence providing an insight into the molecular and cellular mechanisms that contribute to tendon aging and degeneration. Our findings may aid the development of cell-based therapies for tendon repair.


Tendon-derived stem cells Senescence Cell proliferation Transforming growth factor β2 CITED2 



This study was supported by the Fund of Medical Research Foundation of Nanjing Military (ZD04).

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Chao Hu
    • 1
  • Yan Zhang
    • 1
  • Kanglai Tang
    • 2
  • Yuchun Luo
    • 1
    Email author
  • Yunpeng Liu
    • 1
  • Wan Chen
    • 2
  1. 1.Department of Orthopedics101st Hospital of PLAWuxiChina
  2. 2.Department of Orthopedics, Southwest HospitalThird Military Medical UniversityChongqingChina

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