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Osteoarthritis is the most prevalent form of arthritis in the world. Certain signaling pathways, such as the wnt pathway, are involved in cartilage pathology. Osteoarthritic chondrocytes undergo morphological and biochemical changes that lead to chondrocyte de-differentiation. We investigated whether the Wnt pathway is involved in de-differentiation of human articular chondrocytes in vitro. Human articular chondrocytes were cultured for four passages in the presence or absence of IL-1 in monolayer or micromass culture. Changes in cell morphology were monitored by light microscopy. Protein and gene expression of chondrocyte markers and Wnt pathway components were determined by Western blotting and qPCR after culture. After culturing for four passages, chondrocytes exhibited a fibroblast-like morphology. Collagen type II and aggrecan protein and gene expression decreased, while collagen type I, matrix metalloproteinase 13, and nitric oxide synthase expressions increased. Wnt molecule expression profiles changed; Wnt5a protein expression, the Wnt target gene, c-jun, and in Wnt pathway regulator, sFRP4 increased. Treatment with IL-1 caused chondrocyte morphology to become more filament-like. This change in morphology was accompanied by extinction of col II expression and increased col I, MMP13 and eNOS expression. Changes in expression of the Wnt pathway components also were observed. Wnt7a decreased significantly, while Wnt5a, LRP5, β-catenin and c-jun expressions increased. Culture of human articular chondrocytes with or without IL-1 not only induced chondrocyte de-differentiation, but also changed the expression profiles of Wnt components, which suggests that the Wnt pathway is involved in chondrocyte de-differentiation in vitro. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Notch pathway plays a pivotal role in cell fate determination. There is much interest surrounding its therapeutic potential, in osteoarthritis, but the expression profile of Notch-related molecules, as well as their relation with cartilage pathological parameters, remains unclear. The purpose of our study is to analyze the expression pattern of Notch family members, type II and type I collagen, in normal (healthy) and osteoarthritic human knee cartilage. Osteoarthritic cartilages were obtained from 3 patients undergoing a total knee replacement. Macroscopically normal cartilage was dissected from 3 human knees at the time of autopsy or surgery. Immunohistochemical staining was performed using Notch1,2,3 and 4, Delta, Jagged, type II collagen and type I collagen antibodies. In healthy cartilage, type II collagen was abundantly expressed while type I was absent. This latter increased proportionally to the osteoarthritic grade. Type II collagen expression remained intense in osteoarthritic cartilage. In healthy cartilage as well as in cartilage with minor lesions, Notch family member''s proteins were not or just weakly expressed at the surface and in the cells. However, Notch molecules were over-expressed in osteoarthritic cartilage compared to healthy one. This expression pattern was different according to the cartilage zone and the severity of OA. Our data suggest that Notch signaling is activated in osteoarthritic cartilage, compared to healthy cartilage, with a much more abundant expression in the most damaged areas. [Copyright &y& Elsevier]