Resistin targets TAZ to promote osteogenic differentiation through PI3K/AKT/mTOR pathway
JingJing Shang,
Zhentang Yu,
Chengwei Xiong,
Junjie Zhang,
Jinhong Gong,
Changlin Yu,
Yong Huang,
Xindie Zhou
Affiliations
JingJing Shang
Department of Pharmacy, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, China; Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu 213000, China
Zhentang Yu
Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, China; Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu 213000, China; Department of Graduate School, Dalian Medical University, Dalian, Liaoning 116000, China
Chengwei Xiong
Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, China; Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu 213000, China
Junjie Zhang
Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, China; Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu 213000, China
Jinhong Gong
Department of Pharmacy, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, China; Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu 213000, China
Changlin Yu
Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, China; Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu 213000, China
Yong Huang
Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, China; Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu 213000, China
Xindie Zhou
Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, China; Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu 213000, China; Department of Orthopedics, Gonghe County Hospital of Traditional Chinese Medicine, Hainan Tibetan Autonomous Prefecture, Qinghai 811800, China; Corresponding author
Summary: Osteogenic differentiation (OD) of bone marrow mesenchymal stem cells (BMSCs) contributes significantly to the regeneration of bone defects. Resistin, an adipose tissue-specific secretory factor, has been shown to involve many different functions, including metabolism, inflammation, cancer, and bone remodeling. However, the effects and mechanisms of resistin on OD of BMSCs remain unclear. Herein, we demonstrated that resistin was highly expressed in BMSCs with OD. Upregulation of resistin contributed to the progression of OD of BMSCs by activating PI3K/AKT/mTOR signaling pathway. In addition, resistin facilitated OD by targeting transcriptional co-activator with PDZ-binding motif (TAZ). In a rat femoral condyle bone defect model, local injection of resistin significantly promoted bone repair and improved bone formation. This work contributes to better understanding the mechanism of resistin directly involved in the OD and might provide a new therapeutic strategy for bone defect regeneration.
