Abstract：
Type 2 diabetes mellitus (T2DM) can lead to multiple complications. T2DM-related bone damage has been linked to abnormal bone turnover, but it cannot fully explain the mechanisms of T2DM bone disease. This study attempts to elucidate the underlying mechanisms of poor bone quality in T2DM. Hence, T2DM model was induced by a high-fat diet combined with a single streptozotocin injection in 7-week-old male SD rats. Osteoblasts derived from SD rats were cultured in high glucose to mimic hyperglycemia. Low bone turnover was observed in T2DM bone with elevated levels of advanced glycation end-products (AGEs) and receptor for AGEs (RAGE). Additionally, higher levels of oxidative stress and inflammatory factors were found in T2DM bone. AGEs content in bone was pairwise correlated with RAGE, hydrogen peroxide, and inflammatory factors. Serum levels of RAGE, oxidative stress, and inflammatory factors were higher in T2DM, while AGEs content tended to be lower. Besides, 35 differentially expressed metabolites were screened in T2DM serum. Osteoblasts exposed to high glucose displayed analogous abnormal changes in these biomarkers. Thus, low bone turnover in T2DM might be partially due to excess oxidative stress and inflammation induced by AGE-RAGE signaling. Furthermore, these biomarker levels in serum were mostly consistent with bone, demonstrating their possibility for predicting bone quality in T2DM.
摘要：
2型糖尿病(T2DM)可导致多种并发症。T2DM相关的骨损伤与骨转换异常有关，但不能完全解释T2DM骨病的发病机制。本研究试图阐明T2DM中骨质量差的潜在机制。因此，在7周龄雄性SD大鼠中，通过高脂饮食结合单次注射链脲佐菌素诱导T2DM模型。将来自SD大鼠的成骨细胞在高糖中培养以模拟高血糖。在晚期糖基化终产物（AGEs）和AGEs受体（RAGE）水平升高的T2DM骨中观察到低骨转换。此外,2型糖尿病骨组织中存在较高水平的氧化应激和炎症因子。骨中AGEs含量与RAGE成对相关，过氧化氢,和炎症因子。RAGE的血清水平，氧化应激，2型糖尿病患者的炎症因子水平较高,而AGEs含量往往较低。此外,在T2DM血清中筛选出35种差异表达的代谢物。暴露于高葡萄糖的成骨细胞在这些生物标志物中表现出类似的异常变化。因此，T2DM的低骨转换可能部分归因于AGE-RAGE信号诱导的过度氧化应激和炎症。此外，血清中的这些生物标志物水平与骨骼大多一致，证明了它们预测T2DM骨质量的可能性。
