Glycation reactions resulting in the generation and accumulation of advanced glycation endproducts (AGEs) are potential mechanisms by which bone protein may be altered in vivo. AGEs accumulate in the bone increasingly with age come into close contact with osteoblasts or osteoclasts. The direct effect of AGEs on bone cells has not been thoroughly investigated. This study aimed to examine whether glycated bovine serum albumin (AGE - BSA) as an AGE modulate the mRNA expression of various genes in primary human osteoblast cultures. The following parameters were included: RAGE (receptor for AGEs), alkaline phosphatase, osteocalcin, osterix and RANKL (receptor activator of nuclear factor-kappaB ligand). Primary human osteoblast cultures were obtained from bone specimens of six patients with osteoarthrosis. Human osteoblasts were treated in AGE - BSA or control-BSA (non-glycated BSA) containing medium (5 mg/ml each) over a time course of seven days. After RT-PCR the mRNA expression was measured by real-time PCR. Related to control - BSA exposure, the mRNA expression of RAGE, RANKL and osterix increased during AGE - BSA treament. For alkaline phosphatase and osteocalcin a tendency of down-regulation was found. In summary, the study presents evidence that advanced glycation end products accumulated in bone alter osteoblasts by activation the AGE - RAGE pathway (RAGE mRNA up-regulation), inducing enhanced osteoclastogenesis (RANKL mRNA up-regulation) and impaired matrix mineralization (down-regulation of alkaline phosphatase and osteocalcin mRNA). Thus, AGEs may play a functional role in the development of bone diseases (e.g. osteoporosis).

译文

糖基化反应导致高级糖基化终产物 (AGEs) 的产生和积累是体内改变骨蛋白的潜在机制。随着年龄的增长,年龄在骨中的积累越来越多地与成骨细胞或破骨细胞密切接触者。年龄对骨细胞的直接影响尚未得到彻底研究。这项研究旨在检查糖化牛血清白蛋白 (AGE - BSA) 是否作为年龄调节原代人成骨细胞培养物中各种基因的mRNA表达。包括以下参数: RAGE (AGEs受体),碱性磷酸酶,骨钙素,osterix和RANKL (核因子-κ b配体的受体激活剂)。从6例骨关节炎患者的骨标本中获得了原代人成骨细胞培养物。在7天的时间过程中,在含有AGE-BSA或对照-BSA (非糖化BSA) 的培养基 (每个5 mg/ml) 中治疗人成骨细胞。Rt-pcr后,通过实时PCR测量mRNA表达。与对照-BSA暴露有关,RAGE,RANKL和osterix的mRNA表达在年龄-BSA治疗期间增加。对于碱性磷酸酶和骨钙素,发现有下调的趋势。总而言之,该研究提供了证据,表明在骨中积累的高级糖基化终产物通过激活AGE-RAGE途径 (RAGE mRNA上调),诱导破骨细胞生成增强 (RANKL mRNA上调) 和基质矿化受损 (下调碱性磷酸酶和骨钙素mRNA) 来改变成骨细胞。因此,年龄可能在骨骼疾病 (例如骨质疏松症) 的发展中起功能作用。

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