Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
Tianjin Key Laboratory for Advanced Mechatronic System Design and Intelligent Control, National Demonstration Center for Experimental Mechanical and Electrical Engineering Education, School of Mechanical Engineering, Tianjin University of Technology, Tianjin, China.
FASEB J. 2024 Aug 15;38(15):e23871. doi: 10.1096/fj.202400790R.
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.
2 型糖尿病（T2DM）可导致多种并发症。T2DM 相关的骨骼损伤与异常的骨转换有关，但不能完全解释 T2DM 骨骼疾病的机制。本研究试图阐明 T2DM 骨质量差的潜在机制。因此，在 7 周龄雄性 SD 大鼠中通过高脂肪饮食联合单次链脲佐菌素注射诱导 T2DM 模型。将 SD 大鼠的成骨细胞在高葡萄糖中培养以模拟高血糖。T2DM 骨中观察到低骨转换，高水平的晚期糖基化终产物（AGEs）和 AGEs 受体（RAGE）。此外，T2DM 骨中还发现了更高水平的氧化应激和炎症因子。骨中 AGEs 的含量与 RAGE、过氧化氢和炎症因子呈两两相关。T2DM 患者血清中的 RAGE、氧化应激和炎症因子水平较高，而 AGEs 含量趋于降低。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显示这些生物标志物也存在类似的异常变化。因此，T2DM 中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，血清中这些生物标志物水平与骨骼基本一致，表明它们有可能预测 T2DM 中的骨质量。
