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.
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DOI：
10.1016/j.yexcr.2019.111757
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发表时间：
2020-02-15
影响因子：
3.7
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Wang Z;Tang J;Li Y;Wang Y;Guo Y;Tu Q;Chen J;Wang C
糖尿病性骨缺损可能表现出软骨内成骨（ECO）受损，导致骨修复延迟。AdipoRon是脂联素聚合物的受体激动剂，可以改善糖尿病及其相关并发症，并克服人工脂联素聚合物结构不稳定的缺点。在这里，探讨了AdipoRon对糖尿病环境中软骨细胞存活和分化的影响，重点关注基因和蛋白质水平的相关机制。在体内，AdipoRon应用于饮食诱导的肥胖（DIO）小鼠，肥胖和2型糖尿病的模型，股骨骨折。随后进行组织学评价和显微CT检查以进一步验证。我们发现AdipoRon可以通过激活ERK 1/2途径改善高糖培养条件下ATDC 5细胞的存活率、凋亡和活性氧（ROS）产生，并促进软骨形成标志物mRNA表达和软骨基质产生。此外，胃内AdipoRon给药的DIO小鼠有更多的新软骨和加速新骨形成。这些数据表明，AdipoRon可以通过ECO刺激糖尿病患者的骨再生。
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.
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