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The pathological hallmark of rheumatoid arthritis (RA) is a synovial pannus that comprises proliferating and invasive fibroblast-like synoviocytes, infiltrating inflammatory cells, and an associated neoangiogenic response. Animal models have been established to study these pathological features of human RA. Spontaneous and induced animal models of RA primarily reflect inflammatory aspects of the disease. Among various induced animal models, collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA) models are widely used to study the pathogenesis of RA. Improved transplantation techniques for severe combined immunodeficiency (SCID) mouse models of RA can be used to evaluate the effectiveness of potential therapeutics in human tissues and cells. This review provides basic information on various animal models of RA, including CIA and CAIA. In addition, we describe a SCID mouse coimplantation model that can measure the long-distance migration of human RA synoviocytes and cartilage destruction induced by these cells.

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Background High-temperature requirement serine protease A 2 (HtrA2) is known to be involved in growth, unfolded protein response to stress, and apoptosis or autophagy. However, whether HtrA2 controls inflammation and immune response remains elusive. Results Here, we found that the concentration of HtrA2 was elevated in rheumatoid arthritis (RA) synovial fluid (SF) than in osteoarthritis (OA) SF, and its concentrations were correlated with immune cells counts in the RA SF. Strikingly, in the SF of RA patients, HtrA2 levels were elevated in proportion to synovitis severity and correlated with proinflammation cytokines and chemokines, such as IL-8, IL-6 and CCL2. Of note, HtrA2 was highly expressed in RA synoviums and primary synoviocytes. RA synoviocytes released HtrA2 when stimulated by ER stress inducers. Moreover, knockdown of HtrA2 inhibited IL1β-, TNFα- or LPS-induced release of proinflammatory cytokine and chemokine by RA synoviocytes. Conclusion HtrA2 is a novel inflammatory mediator and therefore a promising target for developing an anti-inflammation therapy for RA.

Background: High-temperature requirement serine protease A 2 (HtrA2) is known to be involved in growth, unfolded protein response to stress, and apoptosis or autophagy. However, whether HtrA2 controls inflammation and immune response remains elusive. Results: Here, we found that the concentration of HtrA2 was elevated in rheumatoid arthritis (RA) synovial fluid (SF) than in osteoarthritis (OA) SF, and its concentrations were correlated with immune cells counts in the RA SF. Strikingly, in the SF of RA patients, HtrA2 levels were elevated in proportion to synovitis severity and correlated with proinflammation cytokines and chemokines, such as IL-8, IL-6 and CCL2. Of note, HtrA2 was highly expressed in RA synoviums and primary synoviocytes. RA synoviocytes released HtrA2 when stimulated by ER stress inducers. Moreover, knockdown of HtrA2 inhibited IL1β-, TNFα- or LPS-induced release of proinflammatory cytokine and chemokine by RA synoviocytes. Conclusion: HtrA2 is a novel inflammatory mediator and therefore a promising target for developing an anti-inflammation therapy for RA.