Chronic ingestion of advanced glycation end products induces degenerative spinal changes and hypertrophy in aging pre-diabetic mice.
Chronic ingestion of advanced glycation end products induces degenerative spinal changes and hypertrophy in aging pre-diabetic mice.
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DOI：
10.1371/journal.pone.0116625
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Iatridis JC
中科院分区：
文献类型：
--
作者：
Illien-Jünger S;Lu Y;Qureshi SA;Hecht AC;Cai W;Vlassara H;Striker GE;Iatridis JC
椎间盘（IVD）退行性变和脊柱病理性变化是背痛的主要原因，而背痛是全球残疾的首要原因。肥胖和糖尿病患者患背痛和肌肉骨骼并发症的风险增加。现代饮食含有高水平的晚期糖基化终产物（AGEs），细胞毒性成分，已知这些成分是肥胖、糖尿病和加速衰老病理学的贡献者。关于富含AGE的饮食对脊柱病理学的潜在影响的信息很少，这可能是肥胖和糖尿病患者常见的背痛的原因。本研究调查了特定AGE前体（例如，甲基甘氨酸衍生物（MG））对老龄C57 BL 6小鼠IVD和脊椎病理学的作用，这些小鼠喂食等热量饮食，其中含有标准（dMG+）或减少量的MG衍生物（dMG-;含有60-70%的dMG）。dMG+小鼠表现出糖尿病前期表型，因为它们是胰岛素抗性的但不是高血糖的。dMG+小鼠的椎体显示皮质厚度和皮质面积增加，更多的MG-AGE积聚和椎体终板异位钙化。相对于dMG-小鼠，dMG+小鼠的IVD形态表现出异位钙化、肥大分化和糖胺聚糖损失。总的来说，长期暴露于饮食AGEs促进年龄加速的IVD变性和椎体改变，涉及异位钙化，其与胰岛素抵抗平行发生，并与dMG饮食预防。这项研究描述了一种新的饮食诱导的脊柱退行性变的小鼠模型，结果支持以下假设，即慢性AGE摄入可能是导致糖尿病前期状态、脊柱组织异位钙化和肌肉骨骼并发症的一个因素，这些并发症更常见于慢性糖尿病。
Intervertebral disc (IVD) degeneration and pathological spinal changes are major causes of back pain, which is the top cause of global disability. Obese and diabetic individuals are at increased risk for back pain and musculoskeletal complications. Modern diets contain high levels of advanced glycation end products (AGEs), cyto-toxic components which are known contributors to obesity, diabetes and accelerated aging pathologies. There is little information about potential effects of AGE rich diet on spinal pathology, which may be a contributing cause for back pain which is common in obese and diabetic individuals. This study investigated the role of specific AGE precursors (e.g. methylglyoxal-derivatives (MG)) on IVD and vertebral pathologies in aging C57BL6 mice that were fed isocaloric diets with standard (dMG+) or reduced amounts of MG derivatives (dMG-; containing 60-70% less dMG). dMG+ mice exhibited a pre-diabetic phenotype, as they were insulin resistant but not hyperglycemic. Vertebrae of dMG+ mice displayed increased cortical-thickness and cortical-area, greater MG-AGE accumulation and ectopic calcification in vertebral endplates. IVD morphology of dMG+ mice exhibited ectopic calcification, hypertrophic differentiation and glycosaminoglycan loss relative to dMG- mice. Overall, chronic exposure to dietary AGEs promoted age-accelerated IVD degeneration and vertebral alterations involving ectopic calcification which occurred in parallel with insulin resistance, and which were prevented with dMG- diet. This study described a new mouse model for diet-induced spinal degeneration, and results were in support of the hypothesis that chronic AGE ingestion could be a factor contributing to a pre-diabetic state, ectopic calcifications in spinal tissues, and musculoskeletal complications that are more generally known to occur with chronic diabetic conditions.
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影响因子：
2.8
作者：
Hristova, Gergana I.;Jarzem, Peter;Mwale, Fackson
通讯作者：
Mwale, Fackson
DOI：
10.1007/s00198-013-2319-4
发表时间：
2013-09
期刊：
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
影响因子：
--
作者：
Karim L;Tang SY;Sroga GE;Vashishth D
通讯作者：
Vashishth D
影响因子：
7.7
作者：
He, CJ;Sabol, J;Vlassara, H
通讯作者：
Vlassara, H
影响因子：
3.7
作者：
Illien-Junger S;Grosjean F;Laudier DM;Vlassara H;Striker GE;Iatridis JC
通讯作者：
Iatridis JC
影响因子：
1.9
作者：
Kilpadi, K. L.;ElDabaje, R.;Fajardo, R. J.
通讯作者：
Fajardo, R. J.