Kubomura Daiki, Ueno Tomoya, Yamada Masanori, Nagaoka Isao
Yaizu Suisankagaku Industry Co., Ltd., Yaizu, Shizuoka 425-8570, Japan.
Department of Host Defense and Biochemical Research, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
Exp Ther Med. 2017 Oct;14(4):3137-3144. doi: 10.3892/etm.2017.4849. Epub 2017 Jul 28.
It has been demonstrated that oral administration of N-acetylglucosamine (GlcNAc) alleviates the symptoms of osteoarthritis (OA). The aim of the present study was to elucidate the molecular mechanisms for the chondroprotective action of GlcNAc in OA. Biomarkers for type II collagen degradation and synthesis were evaluated, as were histopathological changes, using a rat anterior cruciate ligament transection (ACLT)-induced OA model. Changes in the expression of genes in the cartilage were assessed via DNA microarray and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The results indicated that ACLT induced histopathological changes of articular cartilage, whereas oral administration of GlcNAc (1,000 mg/kg/day for 28 days) significantly suppressed these changes. Additionally, GlcNAc significantly decreased levels of a type II collagen degradation marker in sera compared with that in the ACLT group, although there were no significant changes in the levels of a type II collagen synthesis marker. Furthermore, DNA microarray and reverse transcription-quantitative polymerase chain reaction results demonstrated that GlcNAc treatment downregulated the expression of periostin, which is likely involved in the degradation of cartilage, whereas GlcNAc upregulated the expression of lipocalin 2, which is involved in the regulation of chondrocyte proliferation and differentiation. In conclusion, the results of the present study suggest that GlcNAc is able to suppress the histopathological changes induced by OA and exhibits a chondroprotective action by inhibiting type II collagen degradation in the articular cartilage, possibly via modulation of the expression of inflammatory and chondroprotective molecules, including periostin and lipocalin 2.
已证实口服N-乙酰葡糖胺(GlcNAc)可减轻骨关节炎(OA)的症状。本研究的目的是阐明GlcNAc在OA中软骨保护作用的分子机制。使用大鼠前交叉韧带横断(ACLT)诱导的OA模型,评估了II型胶原降解和合成的生物标志物以及组织病理学变化。通过DNA微阵列和逆转录定量聚合酶链反应(RT-qPCR)评估软骨中基因表达的变化。结果表明,ACLT诱导了关节软骨的组织病理学变化,而口服GlcNAc(1000 mg/kg/天,持续28天)显著抑制了这些变化。此外,与ACLT组相比,GlcNAc显著降低了血清中II型胶原降解标志物的水平,尽管II型胶原合成标志物的水平没有显著变化。此外,DNA微阵列和逆转录定量聚合酶链反应结果表明,GlcNAc处理下调了骨膜蛋白的表达,骨膜蛋白可能参与软骨降解,而GlcNAc上调了lipocalin 2的表达,lipocalin 2参与软骨细胞增殖和分化的调节。总之,本研究结果表明,GlcNAc能够抑制OA诱导的组织病理学变化,并通过抑制关节软骨中II型胶原的降解发挥软骨保护作用,可能是通过调节包括骨膜蛋白和lipocalin 2在内的炎症和软骨保护分子的表达来实现的。