Evaluating the Similarity of Different Collagen-Induced Arthritis Models to the Pre-Clinical Phase of RA in Female Rats.

Abstract

Since the development of RA is a multistep process, it is critical to take action to prevent RA in the pre-clinical phase. Animal models are currently one of the important methods to study RA, but there are very few animal models for studying the pre-clinical phase of RA (Pre-RA). This study aimed to evaluate the similarity of different collagen-induced arthritis models to Pre-RA in rats.Three types of collagen-induced arthritis (CIA) were as follows: (i) standard collagen-induced group (Std-CIA), injected with 200μg type II collagen at day 0 and 100μg type II collagen at day 7; (ii) single collagen-induced group (Mono-CIA), injected with 200μg type II collagen at day 0; (iii) half-dose collagen-induced group (Half-CIA), injected with 100μg type II collagen at day 0 and 50μg type II collagen at day 7. Arthritis score, hind paw swelling, serum antibodies, and inflammatory cytokines were measured every 7days. Gut microbiota analyses were performed on days 0, 11, 21, 28, and 35. Pain threshold measurement, digital radiography, and joint pathology were also assessed.Both Std-CIA and Mono-CIA could successfully cause RA symptoms, including joint swelling and bone erosion, Half-CIA induced only mild swelling in rats. Serum autoantibodies (anti-CCP and anti-CoII) showed no difference among the three types of CIA models, and so did the pain threshold at day 42. In addition, the pathological changes of joint tissues in the Mono-CIA group were the slightest among the collagen-immunized groups. Gut microbiota analysis demonstrated that Half-CIA could impose similar effects on upregulating genus Prevotella as Std-CIA, but Mono-CIA was weaker than them in rats.According to the characteristics of pre-RA, the Half-CIA model is the best suitable animal model for pre-RA among three types of CIA models in rats and can be a valuable model for pre-RA research.