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Establishment of an in vitro three‐dimensional model for cartilage damage in rheumatoid arthritis
Author(s) -
Peck Yvonne,
Leom Li Ting,
Low Pei Fen Patricia,
Wang DongAn
Publication year - 2018
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.2399
Subject(s) - cartilage , aggrecan , chondrocyte , rheumatoid arthritis , type ii collagen , arthritis , pathology , in vivo , inflammation , immunostaining , matrix metalloproteinase , immunology , osteoarthritis , chemistry , medicine , biology , immunohistochemistry , anatomy , biochemistry , alternative medicine , articular cartilage , microbiology and biotechnology
Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to progressive joint destruction. To further understand the process of rheumatoid cartilage damage, an in vitro model consisting of an interactive tri‐culture of synovial fibroblasts (SFs), LPS‐stimulated macrophages and a primary chondrocyte‐based tissue‐engineered construct was established. The tissue‐engineered construct has a composition similar to that of human cartilage, which is rich in collagen type II and proteoglycans. Data generated from this model revealed that healthy chondrocytes were activated in the presence of SFs and macrophages. The activated chondrocytes subsequently displayed aberrant behaviours as seen in a disease state such as increased apoptosis, decreased gene expression for matrix components such as type II collagen and aggrecan, increased gene expression for tissue‐degrading enzymes (MMP‐1, ‐3, ‐13 and ADAMTS‐4, ‐5), and upregulation of inflammatory mediator gene expression (TNF‐α, IL‐1β, IL‐6 and IKBKB). Additionally, the inclusion of SFs and macrophages in the model enabled both cell types to more closely replicate an in vivo role in mediating cartilage destruction. This is evidenced by extensive matrix loss, detected in the model through immunostaining and biochemical analysis. Subsequent drug treatment with celecoxib has shown that the model was able to respond to the therapeutic effects of this drug by reversing cartilage damage. This study showed that the model was able to recapitulate certain pathological features of an RA cartilage. If properly validated, this model potentially can be used for screening new therapeutic drugs and strategies, thereby contributing to the improvement of anti‐rheumatic treatment. Copyright © 2017 John Wiley & Sons, Ltd.