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中文摘要：
背景：晚期糖基化终末产物对破骨细胞骨吸收功能的影响存在争议,既往多数研究认为其可促进骨吸收,然而另有研究表明其对骨吸收可能呈现抑制效果,但具体机制不清。目的：探究晚期糖基化终末产物对破骨细胞溶解无机骨基质和降解有机骨成分能力的影响及其产生机制。方法：以RANKL对破骨前体细胞RAW 264.7进行定向诱导,在诱导同时加入50-400 mg/L的晚期糖基化终末产物或100 mg/L的牛血清白蛋白,通过观察骨吸收板上溶解坑面积及组织蛋白酶K的表达情况来评估晚期糖基化终末产物对破骨细胞骨吸收功能的影响;并进一步计数抗酒石酸酸性磷酸酶阳性多核细胞数量、计算破骨细胞所含细胞核的数量和检测整合素ανβ3的表达情况。结果与结论：（1）晚期糖基化终末产物组的吸收坑面积和组织蛋白酶K表达量较正常破骨细胞诱导组显著减少,且抑制程度随晚期糖基化终末产物浓度的增高而加重;（2）抗酒石酸酸性磷酸酶染色亦显示抗酒石酸酸性磷酸酶阳性多核细胞数量随晚期糖基化终末产物浓度的增高而显著下降,所含细胞核数量亦减少;（3）实时定量PCR发现整合素ανβ3表达水平随晚期糖基化终末产物作用时间的延长而显著下降;（4）综上结果表明,晚期糖基化终末产物可全面抑制破骨细胞对无机及有机骨基质的吸收功能,其机制可能与晚期糖基化终末产物抑制破骨前体细胞的定向分化、细胞融合及减弱破骨细胞的迁移黏附作用有关。
英文摘要：
BACKGROUND： The effects of advanced glycation end products（AGEs） on osteoclast-induced bone resorption is controversial and the underlying mechanisms remain unclear. Most of the studies indicate that AGEs can enhance bone resorption, while some others show the opposite effects. OBJECTIVE： To investigate the effects of AGEs on osteoclast-induced inorganic matrix dissolution and organic component degradation and the underlying mechanisms. METHODS： RAW 264.7 cells were induced to generate osteoclasts, and AGEs（50-400 μg/mL） or control-bovine serum albumin（100 μg/mL） was added since the beginning of the induction. The effect of AGEs on bone resorption was evaluated by analyzing the area of resorption pits on the Osteo Assay Surface plates and the expression of cathepsin K. Furthermore, the number of tartrate-resistant acid phosphatase（TRAP）-positive multinucleated cells, nuclei per osteoclasts and the expression of integrin α_νβ_3 were detected. RESULTS AND CONCLUSION： The area of resorption pits and expression of cathepsin K in AGEs groups were significantly decreased compared with the control group, and this inhibiting effect became more obvious with the increase of AGEs concentration. TRAP staining also showed that number of TRAP-positive multinucleated cells and nuclei per osteoclast were significantly reduced in an AGE dose-dependent manner. Quantitative PCR revealed that the expression of integrin α_νβ_3 decreased significantly with the extension of AGEs incubation time. These data indicate that AGEs can exert inhibitory effects on organic and inorganic matrix degradation induced by osteoclasts. The underlying mechanism may be involved in the inhibitory effects of AGEs on directed differentiation and cell fusion of osteoclast precursor cells, and migration and adhension of osteoclasts.
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