Takase Fumiaki, Mifune Yutaka, Inui Atsuyuki, Ueda Yasuhiro, Kataoka Takeshi, Kokubu Takeshi, Kuroda Ryosuke
Department of Orthopedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
J Orthop Surg Res. 2018 Jun 7;13(1):143. doi: 10.1186/s13018-018-0848-4.
Advanced glycation end products are associated with aging, hyperglycemia, and oxidative stress. Accumulation of advanced glycation end products can cause various pathological conditions; however, the association of Dupuytren's disease with advanced glycation end products has not been demonstrated yet. The aim of this study is to investigate the association of Dupuytren's disease with advanced glycation end products.
Normal palmar fascia from five patients with carpal tunnel syndrome (control group) and Dupuytren's cords from five patients (Dupuytren's disease group) were harvested. The tissues were stained using an anti-advanced glycation end products antibody, anti-receptor for advanced glycation end products antibody, and an anti-reactive oxygen species modulator 1 antibody. The expression of nicotinamide adenine dinucleotide phosphate oxidase-1 and nicotinamide adenine dinucleotide phosphate oxidase-4 genes was also assessed using real-time PCR. For in vitro analysis, the cells harvested from the control and Dupuytren's disease groups were used. After 3 days of exposure to four types of media (control group, control + advanced glycation end products group, Dupuytren's disease group, Dupuytren's disease + advanced glycation end products group), superoxide detection reagent was detected using a total reactive oxygen species/superoxide detection kit.
Immunostaining of the palmar fasciae of the Dupuytren's disease group showed higher expressions of advanced glycation end products and receptor for advanced glycation end products than that in the control group. The expression of nicotinamide adenine dinucleotide phosphate oxidase oxidase-1 and nicotinamide adenine dinucleotide phosphate oxidase-4 as well as reactive oxygen species modulator 1, an oxidatively damaged protein, was also higher in the Dupuytren's disease group than in the control group. In an in vitro cell culture, the addition of advanced glycation end products to the Dupuytren's disease-derived cells produced more superoxide free radicals.
These data suggest that the advanced glycation end products receptor for advanced glycation end products interaction produced free radicals via nicotinamide adenine dinucleotide phosphate oxidase activation in Dupuytren's disease patients. Further studies are required to confirm these results.
晚期糖基化终产物与衰老、高血糖和氧化应激相关。晚期糖基化终产物的积累可导致多种病理状况;然而,掌腱膜挛缩症与晚期糖基化终产物之间的关联尚未得到证实。本研究的目的是调查掌腱膜挛缩症与晚期糖基化终产物之间的关联。
采集5例腕管综合征患者的正常掌腱膜(对照组)和5例掌腱膜挛缩症患者的掌腱膜条索(掌腱膜挛缩症组)。使用抗晚期糖基化终产物抗体、抗晚期糖基化终产物受体抗体和抗活性氧调节剂1抗体对组织进行染色。还使用实时聚合酶链反应评估烟酰胺腺嘌呤二核苷酸磷酸氧化酶-1和烟酰胺腺嘌呤二核苷酸磷酸氧化酶-4基因的表达。对于体外分析,使用从对照组和掌腱膜挛缩症组采集的细胞。在暴露于四种类型的培养基3天后(对照组、对照组 + 晚期糖基化终产物组、掌腱膜挛缩症组、掌腱膜挛缩症 + 晚期糖基化终产物组),使用总活性氧/超氧化物检测试剂盒检测超氧化物检测试剂。
掌腱膜挛缩症组掌腱膜的免疫染色显示,晚期糖基化终产物和晚期糖基化终产物受体的表达高于对照组。烟酰胺腺嘌呤二核苷酸磷酸氧化酶-1和烟酰胺腺嘌呤二核苷酸磷酸氧化酶-4以及氧化损伤蛋白活性氧调节剂1在掌腱膜挛缩症组中的表达也高于对照组。在体外细胞培养中,向掌腱膜挛缩症来源的细胞中添加晚期糖基化终产物会产生更多的超氧自由基。
这些数据表明,晚期糖基化终产物受体与晚期糖基化终产物的相互作用通过激活掌腱膜挛缩症患者的烟酰胺腺嘌呤二核苷酸磷酸氧化酶产生自由基。需要进一步研究来证实这些结果。