Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Ishikawa, Japan.
Nutrients. 2022 Feb 26;14(5):990. doi: 10.3390/nu14050990.
In diabetic patients, the metabolism of excess glucose increases the toxicity of the aldehyde group of sugar. Aldehydes, including glyceraldehyde (GA), react with intracellular proteins to form advanced glycation end-products (AGEs), which deteriorate bone quality and cause osteoporosis. One of the causes of osteoporotic fractures is impaired osteoblast osteogenesis; however, the cytotoxic effects of aldehydes and the subsequent formation of AGEs in osteoblasts have not yet been examined in detail. Therefore, the present study investigated the cytotoxicity of intracellular GA and GA-derived AGEs, named toxic AGEs (TAGE), in the mouse osteoblastic cell line MC3T3-E1. Treatment with GA induced MC3T3-E1 cell death, which was accompanied by TAGE modifications in several intracellular proteins. Furthermore, the downregulated expression of Runx2, a transcription factor essential for osteoblast differentiation, and collagen correlated with the accumulation of TAGE. The GA treatment also reduced the normal protein levels of collagen in cells, suggesting that collagen may be modified by TAGE and form an abnormal structure. Collectively, the present results show for the first time that GA and TAGE exert cytotoxic effects in osteoblasts, inhibit osteoblastic differentiation, and decrease the amount of normal collagen. The suppression of GA production and associated accumulation of TAGE has potential as a novel therapeutic target for osteoporosis under hyperglycemic conditions.
在糖尿病患者中，过量葡萄糖的代谢会增加糖醛基的毒性。醛类，包括甘油醛（GA），与细胞内蛋白质反应形成晚期糖基化终产物（AGEs），从而降低骨质量并导致骨质疏松症。骨质疏松性骨折的原因之一是成骨细胞成骨能力受损；然而，醛类的细胞毒性作用以及随后在成骨细胞中形成的 AGEs 尚未详细研究。因此，本研究探讨了细胞内 GA 和 GA 衍生的 AGEs（称为毒性 AGEs [TAGE]）在小鼠成骨细胞系 MC3T3-E1 中的细胞毒性。GA 处理诱导 MC3T3-E1 细胞死亡，同时伴有几种细胞内蛋白质的 TAGE 修饰。此外，转录因子 Runx2 的表达下调，Runx2 是成骨细胞分化所必需的转录因子，与 TAGE 的积累相关。GA 处理还降低了细胞中正常的胶原蛋白蛋白水平，表明胶原蛋白可能被 TAGE 修饰并形成异常结构。总之，这些结果首次表明 GA 和 TAGE 在成骨细胞中具有细胞毒性作用，抑制成骨细胞分化，并减少正常胶原蛋白的含量。抑制 GA 产生和相关 TAGE 积累可能成为高血糖条件下骨质疏松症的一种新的治疗靶点。
