Three-dimensional (3D) in vitro arthritis models for drug screening

Abstract

Arthritis is a chronic joint disorder that cause substantial physical disability therefore increasing drugs had been made to improve the quality of life of arthritis patient. With the increasing concern about the use of animals during pre-clinical studies and limitations of in vitro models such as dedifferentiation, inability to recapitulate the complex 3D structures of native cartilage, an unmet need arises. A novel 3D OA model was previously established using living hyaline cartilage graft (LHCG) to meet the unmet need. The objectives of this project are to test the efficacy of 3D OA model using celecoxib and to establish a novel 3D RA model. Drug treatment on 3D OA model had shown down regulation of catabolic genes such as MMP1, MMP-3 and COX-2 and increase of cell viability upon treatment. In addition, results also show inhibition of nitric oxide (NO) and prostaglandinE2 (PGE2) that are major mediators in cartilage degradation. On the other hand, results of 3D RA model had shown low expression of anabolic genes and high expression of catabolic genes. Staining of proteoglycan and collagen type II had also revealed extensive degradation of cartilage. To conclude, results for drug treatment in novel 3D OA model had prove its efficacy as an accurate model for drug screening and a novel 3D in vitro cartilaginous model for mimicking native RA cartilage has been established.