2. Academic Validation
  3. TRAF4 positively regulates the osteogenic differentiation of mesenchymal stem cells by acting as an E3 ubiquitin ligase to degrade Smurf2

TRAF4 positively regulates the osteogenic differentiation of mesenchymal stem cells by acting as an E3 ubiquitin ligase to degrade Smurf2

  • Cell Death Differ. 2019 Dec;26(12):2652-2666. doi: 10.1038/s41418-019-0328-3.
Jinteng Li # 1 2,  Peng Wang # 1 2,  Zhongyu Xie # 1 2,  Shan Wang 3,  Shuizhong Cen 2,  Ming Li 2,  Wenjie Liu 2,  Su'an Tang 2,  Guiwen Ye 2,  Guan Zheng 2,  Hongjun Su 3,  Mengjun Ma 1 2,  Xiaohua Wu 3,  Yanfeng Wu 4,  Huiyong Shen 5 6
Affiliations

Affiliations

  • 1 Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, P.R. China.
  • 2 Department of Orthopedics, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, P.R. China.
  • 3 Center for Biotherapy, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, P.R. China.
  • 4 Center for Biotherapy, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, P.R. China. wuyf@mail.sysu.edu.cn.
  • 5 Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, P.R. China. shenhuiy@mail.sysu.edu.cn.
  • 6 Department of Orthopedics, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, P.R. China. shenhuiy@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 31076633 DOI: 10.1038/s41418-019-0328-3
Abstract

TNF receptor-associated factor 4 (TRAF4), a member of the TRAF family, plays an important role in the embryogenesis and development of the bone system. Mesenchymal stem cells (MSCs), which are the primary origin of osteoblasts in vivo, are key cells in bone development; however, whether TRAF4 modulates the osteogenic capacity of MSCs has never been explored. In this study, we demonstrated that TRAF4 positively regulates the osteogenic process of MSCs both in vitro and in vivo. In addition, we further demonstrated that TRAF4 modulates the osteogenic process of MSCs by acting as an E3 ubiquitin Ligase to mediate the K48-linked ubiquitination of Smurf2 at the K119 site and cause degradation. Furthermore, TRAF4 was abnormally decreased in bone sections of ovariectomized rat and osteoporosis patients. Taken together, our findings suggest that TRAF4 positively regulates the osteogenic differentiation of MSCs by acting as an E3 ubiquitin Ligase to degrade Smurf2. These results emphasize the critical role of TRAF4 in bone formation and could not only improve the clinical use of MSCs in tissue engineering but also clarify the pathogenesis of bone metabolism disorders.

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