2. Academic Validation
  3. GIT1 contributes to autophagy in osteoclast through disruption of the binding of Beclin1 and Bcl2 under starvation condition

GIT1 contributes to autophagy in osteoclast through disruption of the binding of Beclin1 and Bcl2 under starvation condition

  • Cell Death Dis. 2018 Dec 13;9(12):1195. doi: 10.1038/s41419-018-1256-8.
Shu-Jie Zhao 1,  Fan-Qi Kong 1,  Wei Cai 1 2,  Tao Xu 1,  Zhi-Min Zhou 1,  Zi-Bin Wang 3,  An-Di Xu 4,  Ya-Qing Yang 4,  Jian Chen 1,  Peng-Yu Tang 1,  Qian Wang 1,  Lin Cheng 1,  Yong-Jun Luo 1,  Zheng Zhou 1,  Lin-Wei Li 1,  Yi-Fan Huang 1,  Xuan Zhao 1,  Guo-Yong Yin 5,  Ming-Xin Xue 6,  Jin Fan 7
Affiliations

Affiliations

  • 1 Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, China.
  • 2 Department of Orthopedics, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, 223001, Jiangsu, China.
  • 3 Analytical & Testing Center, Nanjing Medical University, Nanjing, 210000, Jiangsu, China.
  • 4 Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, 210000, Jiangsu, China.
  • 5 Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, China. [email protected].
  • 6 Department of Massage, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, China. [email protected].
  • 7 Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, China. [email protected].
PMID: 30546041 DOI: 10.1038/s41419-018-1256-8
Abstract

Approximately 10-15% of all bone fractures do not heal properly, causing patient morbidity and additional medical care expenses. Therefore, better mechanism-based fracture repair approaches are needed. In this study, a reduced number of osteoclasts (OCs) and autophagosomes/autolysosomes in OC can be observed in GPCR kinase 2-interacting protein 1 (GIT1) knockout (KO) mice on days 21 and 28 post-fracture, compared with GIT1 wild-type (GIT1 WT) mice. Furthermore, in vitro experiments revealed that GIT1 contributes to OC Autophagy under starvation conditions. Mechanistically, GIT1 interacted with Beclin1 and promoted Beclin1 phosphorylation at Thr119, which induced the disruption of Beclin1 and Bcl2 binding under starvation conditions, thereby, positively regulating Autophagy. Taken together, the findings suggest a previously unappreciated role of GIT1 in Autophagy of OCs during fracture repair. Targeting GIT1 may be a potential therapeutic approach for bone fractures.

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