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

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 200 μg type II collagen at day 0 and 100 μg type II collagen at day 7; (ii) single collagen-induced group (Mono-CIA), injected with 200 μg type II collagen at day 0; (iii) half-dose collagen-induced group (Half-CIA), injected with 100 μg type II collagen at day 0 and 50 μg type II collagen at day 7. Arthritis score, hind paw swelling, serum antibodies, and inflammatory cytokines were measured every 7 days. 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.