Quincey Adam, Mohan Subburaman, Edderkaoui Bouchra
Musculoskeletal Disease Center, Research Service, VA Loma Linda Healthcare Systems, Loma Linda, CA 92357, USA.
Department of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
Life (Basel). 2022 Jun 3;12(6):836. doi: 10.3390/life12060836.
Chemokines are secreted by a large variety of cells. They are involved in controlling cell trafficking, maturation, and differentiation. However, the specific responses and effects of chemokines on specific skeletal cell types under high glucose conditions have not been investigated. Chondrocytes play an important role in osteoarthritis and fracture healing. Delayed fracture healing is one of the major health complications caused by diabetes, so the goal of this study was to evaluate the response of several chemokines to high glucose conditions in chondrocyte cells and analyze their role in the catabolic effect of hyperglycemia. ATDC5 chondrocytes were cultured in normal and high glucose media, and mRNA expression levels of several chemokines and chondrocyte differentiation markers were quantified. Bindarit, a specific inhibitor of monocyte chemotactic proteins (MCPs), was used to determine the role of MCPs in mediating the effects of high glucose conditions in chondrocyte cells. High glucose treatment upregulated the expression of three , as well as the expression of matrix metalloproteinase 13 () and Osteocalcin (). Furthermore, bindarit treatment downregulated and but upregulated Collagen 2 ( mRNA levels in chondrocytes treated with high glucose. Moreover, treatment of chondrocytes with ascorbic acid reduced the effect of high glucose conditions on the expression of chemokines and . These data together suggest that MCPs mediate the catabolic effect of high glucose in chondrocytes.
趋化因子由多种细胞分泌。它们参与控制细胞迁移、成熟和分化。然而,尚未研究过高糖条件下趋化因子对特定骨骼细胞类型的具体反应和影响。软骨细胞在骨关节炎和骨折愈合中起重要作用。骨折愈合延迟是糖尿病引起的主要健康并发症之一,因此本研究的目的是评估几种趋化因子在软骨细胞中对高糖条件的反应,并分析它们在高血糖分解代谢作用中的作用。将ATDC5软骨细胞培养在正常和高糖培养基中,并对几种趋化因子和软骨细胞分化标志物的mRNA表达水平进行定量。Bindarit是单核细胞趋化蛋白(MCPs)的特异性抑制剂,用于确定MCPs在介导高糖条件对软骨细胞影响中的作用。高糖处理上调了三种趋化因子的表达,以及基质金属蛋白酶13(MMP13)和骨钙素(OCN)的表达。此外,Bindarit处理下调了高糖处理的软骨细胞中MMP13和OCN的表达,但上调了Ⅱ型胶原蛋白(Col2)的mRNA水平。此外,用抗坏血酸处理软骨细胞可降低高糖条件对趋化因子和OCN表达的影响。这些数据共同表明,MCPs介导了高糖对软骨细胞的分解代谢作用。