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.

中文翻译：

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AdipoRon通过增强软骨细胞的存活和分化能力，通过基于软骨内骨化的骨修复促进糖尿病性骨折修复。

糖尿病性骨缺损可能表现为软骨内骨化（ECO）受损，导致骨修复延迟。脂联素聚合物的受体激动剂AdipoRon可以改善糖尿病和相关并发症，并克服人造脂联素聚合物不稳定结构的缺点。在这里，着重于基因和蛋白质水平的相关机制，探讨了AdipoRon对糖尿病环境中软骨细胞存活和分化的影响。在体内，AdipoRon用于饮食诱发肥胖（DIO）小鼠，一种肥胖和2型糖尿病的股骨骨折模型。进行了连续的组织学评估和显微CT检查，以进行进一步的验证。我们发现AdipoRon可以改善细胞活力，凋亡，通过激活ERK1 / 2途径促进高糖培养基中ATDC5细胞软骨生成标记的mRNA表达和软骨基质生成。此外，给予胃内AdipoRon的DIO小鼠具有更多的新软骨并加速了新骨的形成。这些数据表明，AdipoRon可以通过ECO促进糖尿病中的骨骼再生。