1. Academic Validation
  2. AdipoRon promotes diabetic fracture repair through endochondral ossification-based bone repair by enhancing survival and differentiation of chondrocytes

AdipoRon promotes diabetic fracture repair through endochondral ossification-based bone repair by enhancing survival and differentiation of chondrocytes

  • Exp Cell Res. 2020 Feb 15;387(2):111757. doi: 10.1016/j.yexcr.2019.111757.
Zhongyi Wang 1 Jinxin Tang 1 Ying Li 2 Yu Wang 1 Yanyang Guo 1 Qisheng Tu 3 Jake Chen 4 Chen Wang 5
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Oral Diseases, Department of Prosthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China.
  • 2 Department of Stomatology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, China.
  • 3 Tufts School of Dental Medicine, Sackler School of Graduate Biomedical Sciences, Tufts School of Medicine, Boston, 02111, USA.
  • 4 Tufts School of Dental Medicine, Sackler School of Graduate Biomedical Sciences, Tufts School of Medicine, Boston, 02111, USA. Electronic address: [email protected].
  • 5 Jiangsu Key Laboratory of Oral Diseases, Department of Prosthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China. Electronic address: [email protected].
Abstract

Diabetic bone defects may exhibit impaired endochondral ossification (ECO) leading to delayed bone repair. AdipoRon, a receptor agonist of Adiponectin polymers, can ameliorate diabetes and related complications, as well as overcome the disadvantages of the unstable structure of artificial Adiponectin polymers. Here, the effects of AdipoRon on the survival and differentiation of chondrocytes in a diabetic environment were explored focusing on related mechanisms in gene and protein levels. In vivo, AdipoRon was applied to diet-induced-obesity (DIO) mice, a model of obesity and type 2 diabetes, with femoral fracture. Sequential histological evaluations and micro-CT were examined for further verification. We found that AdipoRon could ameliorate cell viability, Apoptosis, and Reactive Oxygen Species (ROS) production and promote mRNA expression of chondrogenic markers and cartilaginous matrix production of ATDC5 cells in high glucose medium via activating ERK1/2 pathway. Additionally, DIO mice with intragastric AdipoRon administration had more neocartilage and accelerated new bone formation. These data suggest that AdipoRon could stimulate bone regeneration via ECO in diabetes.

Keywords

AdipoRon; Apoptosis; Bone regeneration; Diabetes mellitus; ERK1/2 pathway; Endochondral ossification.

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