title: Establishment of an in vitro three-dimensional model for cartilage damage in rheumatoid arthritis.
abstract: 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.
authors.affiliation: Division of BioEngineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Peck
authors.affiliation: Division of BioEngineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
authors.forename: Li Ting
authors.initials: LT
authors.lastname: Leom
authors.affiliation: Division of BioEngineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
authors.forename: Pei Fen Patricia
authors.initials: PFP
authors.lastname: Low
authors.affiliation: Division of BioEngineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
authors.forename: Dong-An
authors.initials: DA
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000473:pathology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology*; D000068579:Celecoxib / Q000494:pharmacology / Q000627:therapeutic use; D018929:Cell Culture Techniques; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000473:pathology; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D013552:Swine; D013583:Synovial Membrane / Q000473:pathology; D000074084:THP-1 Cells; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D020011:Protective Agents; D000068579:Celecoxib
keywords: cartilage; disease modelling; in vitro RA model; tissue engineering