Sassi N, Laadhar L, Allouche M, Zandieh-Doulabi B, Hamdoun M, Klein-Nulend J, Makni S, Sellami S
Immuno-Rheumatology research laboratory, Rheumatology Department, La Rabta Hospital, University of Tunis-El Manar.
Biotech Histochem. 2014 Jan;89(1):53-65. doi: 10.3109/10520295.2013.819123. Epub 2013 Aug 1.
Osteoarthritis is the most prevalent form of arthritis in the world and it is becoming a major public health problem. Osteoarthritic chondrocytes undergo morphological and biochemical changes that lead to de-differentiation. The involvement of signaling pathways, such as the Wnt pathway, during cartilage pathology has been reported. Wnt signaling regulates critical biological processes. Wnt signals are transduced through at least three intracellular signaling pathways including the canonical Wnt/β-catenin pathway, the Wnt/Ca2 + pathway and the Wnt/planar cell polarity pathway. We investigated the involvement of the Wnt canonical and non-canonical pathways in human articular chondrocyte de-differentiation in vitro. Human articular chondrocytes were cultured through four passages with no treatment, or with sFRP3 treatment, an inhibitor of Wnt pathways, or with DKK1 treatment, an inhibitor of the canonical pathway. Chondrocyte-secreted markers and Wnt pathway components were analyzed using western blotting and qPCR. Inhibition of the Wnt pathway showed that the canonical Wnt signaling probably is responsible for inhibition of collagen II expression, activation of metalloproteinase 13 expression and regulation of Wnt7a and c-jun expression during chondrocyte de-differentiation in vitro. Our results also suggest that expressions of eNOS, Wnt5a and cyclinE1 are regulated by non-canonical Wnt signaling.
骨关节炎是世界上最常见的关节炎形式，并且正成为一个主要的公共卫生问题。骨关节炎软骨细胞会经历导致去分化的形态和生化变化。据报道，在软骨病变过程中信号通路如Wnt通路会参与其中。Wnt信号传导调节关键的生物学过程。Wnt信号通过至少三种细胞内信号通路进行转导，包括经典的Wnt/β-连环蛋白通路、Wnt/Ca2+通路和Wnt/平面细胞极性通路。我们研究了Wnt经典和非经典通路在体外人关节软骨细胞去分化中的作用。人关节软骨细胞未经处理、用Wnt通路抑制剂sFRP3处理或用经典通路抑制剂DKK1处理，培养四代。使用蛋白质印迹法和定量聚合酶链反应分析软骨细胞分泌的标志物和Wnt通路成分。Wnt通路的抑制表明，在体外软骨细胞去分化过程中，经典Wnt信号可能负责抑制胶原蛋白II的表达、激活金属蛋白酶13的表达以及调节Wnt7a和c-jun的表达。我们的结果还表明，内皮型一氧化氮合酶、Wnt5a和细胞周期蛋白E1的表达受非经典Wnt信号调节。
