Njoto Ibrahim, Kalim Handono, Soeatmadji Djoko W, Handono Kusworini, Fatchiyah Fatchiyah
Department of Anatomy, Faculty of Medicine, Wijaya Kusuma University, Surabaya, Indonesia.
Faculty of Medicine, University of Brawijaya, Malang, Indonesia.
Med Arch. 2019 Jun;73(3):144-148. doi: 10.5455/medarh.2019.73.144-148.
Previous research found that diabetes mellitus capable to aggravate osteoarthritis disease. In brief, the hyperglycemia condition in diabetes mellitus has an impact on protein glycation of all joint components, including molecule, such as perlecan. The protein expression of perlecan reflects the presence amount of perlecan in the matrix of articular cartilage. However, the impact of hyperglycemia on articular perlecan has not been explained. Moreover, the role of perlecan as a mechanotransducer for chondrocytes in type 1 Diabetes mellitus remains unclear.
This research aims to analyze the effect of hyperglycemia in type 1 Diabetes mellitus to the mRNA level and protein expression of perlecan.
Thirty-five adult male rats were divided into seven groups, such as three groups of rat model with anterior cruciate ligament transection (ACLT) at right knee (ACLT1, ACLT2, ACLT3); three groups of rats with ACLT at right knee which followed by Streptozotocin injection for diabetic mice model (DM1, DM2, DM3); and control group (N). Rat sacrificed at the third week, fourth week, and sixth week after two months of maintenance. The mRNA level and protein expression were analyzed by using PCR and Western blot. All of data was analyzed by ANOVA.
Protein expression of perlecan in ACLT mice with diabetes mellitus (DM1, DM2, DM3 group) was gradually decreased according to the increased hyperglycemia duration. Whilst, protein expression of perlecan within ACLT mice without diabetes mellitus (ACLT1, ACLT2, ACLT3 group) was increased. The similar result also demonstrated by the mRNA level of perlecan. Group of DM1, DM2, DM3 exhibited decreased mRNA level of perlecan over the hyperglycemia duration. While, ACLT1, ACLT2, and ACLT3 group had a gradually increased of perlecan mRNA level.
Hyperglycemia on osteoarthritic condition decreased mRNA level and protein expression of perlecan which increased the severity of osteoarthritis disease.
先前的研究发现糖尿病能够加重骨关节炎疾病。简而言之，糖尿病中的高血糖状况会影响所有关节成分的蛋白质糖基化，包括分子，如基底膜聚糖。基底膜聚糖的蛋白质表达反映了其在关节软骨基质中的存在量。然而，高血糖对关节基底膜聚糖的影响尚未得到解释。此外，基底膜聚糖作为1型糖尿病中软骨细胞机械转导分子的作用仍不清楚。
本研究旨在分析1型糖尿病中的高血糖对基底膜聚糖mRNA水平和蛋白质表达的影响。
35只成年雄性大鼠分为7组，如3组右膝前交叉韧带横断（ACLT）大鼠模型（ACLT1、ACLT2、ACLT3）；3组右膝ACLT后注射链脲佐菌素建立的糖尿病小鼠模型（DM1、DM2、DM3）；以及对照组（N）。饲养两个月后，分别在第3周、第4周和第6周处死大鼠。通过PCR和蛋白质印迹法分析mRNA水平和蛋白质表达。所有数据采用方差分析。
糖尿病性ACLT小鼠（DM1、DM2、DM3组）中基底膜聚糖的蛋白质表达随着高血糖持续时间的增加而逐渐降低。与此同时，非糖尿病性ACLT小鼠（ACLT1、ACLT2、ACLT3组）中基底膜聚糖的蛋白质表达增加。基底膜聚糖的mRNA水平也呈现出类似结果。DM1、DM2、DM3组在高血糖持续期间基底膜聚糖的mRNA水平降低。而ACLT1、ACLT2和ACLT3组基底膜聚糖mRNA水平逐渐升高。
骨关节炎状态下的高血糖降低了基底膜聚糖的mRNA水平和蛋白质表达，从而增加了骨关节炎疾病的严重程度。
