Contribution of methylglyoxal to delayed healing of bone injury in diabetes
Contribution of methylglyoxal to delayed healing of bone injury in diabetes
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DOI：
10.3892/mmr.2017.6589
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发表时间：
2017-07-01
影响因子：
3.4
通讯作者：
Tsuchiya, Hiroyuki
中科院分区：
文献类型：
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作者：
Aikawa, Takao;Matsubara, Hidenori;Tsuchiya, Hiroyuki
糖尿病患者易发生骨折延迟愈合或假关节。慢性持续性高血糖、葡萄糖代谢的反应性中间衍生物，如甲基乙二醛（MGO）和晚期糖基化终产物（AGEs）与糖尿病并发症有关。在本研究中，研究了MGO是否能够引起糖尿病患者骨愈合紊乱。用链脲佐菌素（50 mg/ kg）连续5 d诱导雄性小鼠糖尿病。左侧股骨远端形成骨缺损（直径1.0 mm），通过计算机断层扫描检查评估骨修复情况。ST2细胞暴露于MGO （0-400 μ M）中，研究成骨细胞分化、细胞活力和损伤。因此，糖尿病小鼠的血糖和血红蛋白A1c水平分别为493 +/- 14.1 mg/dl和8.0 +/- 0.05%。与非糖尿病小鼠相比，糖尿病小鼠的骨愈合明显延迟，血清和股骨中mgo来源的AGEs、n- δ -（羧甲基）赖氨酸和n- δ -（5-氢-5-甲基-4-咪唑酮-2-基）鸟氨酸水平升高。MGO以剂量依赖的方式抑制ST2细胞成骨分化，并通过细胞毒性显著降低细胞增殖。总之，MGO已被证明会导致糖尿病患者成骨细胞分化受损和骨修复延迟。因此，MGO的解毒可能是对抗糖尿病患者骨骼问题的潜在有用策略。
Patients with diabetes are vulnerable to delayed bone fracture healing or pseudoarthrosis. Chronic sustained hyperglycemia, reactive intermediate derivatives of glucose metabolism, such as methylglyoxal (MGO), and advanced glycation end-products (AGEs) are implicated in diabetic complications. In the present study, it was examined whether MGO is able to cause disturbed bone healing in diabetes. Diabetes was induced in male mice by injection of streptozotocin (50 mg/ kg) for 5 days. A bone defect (1.0-mm diameter) was created in the left distal femur, and bone repair was assessed from an examination of computed tomography scans. ST2 cells were exposed to MGO (0-400 mu M) to investigate osteoblastic differentiation, cell viability, and damage. Consequently, blood glucose and hemoglobin A1c levels in diabetic mice were determined to be 493 +/- 14.1 mg/dl and 8.0 +/- 0.05%, respectively. Compared with non-diabetic control mice, diabetic mice exhibited markedly delayed bone healing, with increased levels of the MGO-derived AGEs, N-delta-(carboxymethyl)-lysine and N-delta-(5-hydro-5-methyl-4-imidazolone-2-yl)-ornithine, in the sera and femurs. MGO inhibited the osteoblastic differentiation of ST2 cells in a dose-dependent manner, and markedly decreased cell proliferation through cytotoxicity. In conclusion, MGO has been demonstrated to cause impaired osteoblastic differentiation and delayed bone repair in diabetes. Therefore, detoxification of MGO may be a potentially useful strategy against bone problems in patients with diabetes.