Yokosuka Kimiaki, Park Jin Soo, Jimbo Kotaro, Yamada Kei, Sato Kimiaki, Tsuru Michiyo, Takeuchi Masayoshi, Yamagishi Sho-Ichi, Nagata Kensei
Department of Orthopedic Surgery and Internal Medicine III, Kurume University School of Medicine, Kurume, Japan.
J Neurosurg Spine. 2006 Oct;5(4):324-9. doi: 10.3171/spi.2006.5.4.324.
The authors sought to clarify the role, if any, of advanced glycation end-products (AGEs) in disc degeneration.
Intervertebral discs were analyzed for the presence of AGEs and of their receptor (RAGE) by immunohistochemical analysis. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect any RAGE gene expression, and real-time PCR was used to quantify messenger RNA (mRNA) levels of aggrecan and collagen types I and II in nucleus pulposus cells treated with AGEs. Aggrecan protein concentration was determined by enzyme-linked immunosorbent assay. Immunohistochemical analysis revealed that AGEs and RAGE were localized in the nucleus pulposus of the intervertebral disc. Advanced glycation end-products were found to significantly suppress the expression of aggrecan at both mRNA and protein levels in a dose- and time-dependent manner. The levels of collagen types I and II remained unchanged after treatments with AGEs.
These results suggest that the accumulation of AGEs and their interaction with their receptor in the nucleus pulposus might result in the downregulation of aggrecan production responsible for disc degeneration.
作者试图阐明晚期糖基化终末产物（AGEs）在椎间盘退变中是否发挥作用（若有作用则明确其作用）。
通过免疫组织化学分析检测椎间盘内AGEs及其受体（RAGE）的存在情况。进行逆转录聚合酶链反应（RT-PCR）以检测RAGE基因表达，并用实时PCR定量分析经AGEs处理的髓核细胞中聚集蛋白聚糖以及Ⅰ型和Ⅱ型胶原蛋白的信使核糖核酸（mRNA）水平。采用酶联免疫吸附测定法测定聚集蛋白聚糖蛋白浓度。免疫组织化学分析显示，AGEs和RAGE定位于椎间盘的髓核中。发现晚期糖基化终末产物以剂量和时间依赖性方式显著抑制聚集蛋白聚糖在mRNA和蛋白水平的表达。用AGEs处理后，Ⅰ型和Ⅱ型胶原蛋白水平保持不变。
这些结果表明，AGEs在髓核中的积累及其与受体的相互作用可能导致负责椎间盘退变的聚集蛋白聚糖产生下调。
