A novel mouse model of arthritis with enthesitis and heterotopic ossification

Ankylosing spondylitis (AS), enthesitis-related arthritis, and psoriatic arthritis are autoimmune bone diseases that share the characteristic pathological features of enthesitis and heterotopic ossification. This sets them apart from bone-eroding inflammatory joint diseases such as rheumatoid arthritis. The lack of effective animal models severely hampers the research on their pathogenesis and treatment. Here, we report that a peptide derived from amino acids 91-115 in the G1 domain of the chondroitin sulfate proteoglycan versican potently increases the incidence of type II collagen-induced arthritis in BALB/c mice from less than 20% to over 95%. This novel model, designated the C2V7 model, exhibited key features of these types of arthritis, including enthesitis, arthritis, and extensive ectopic ossification. The joint inflammation level in the C2V7 model was comparable to that in the curdlan-induced SKG model established in BALB/c-ZAP70W163C mice. Moreover, co-administration of the versican peptide with type II collagen exacerbated arthritis in this SKG strain. Notably, the C2V7 model showed a significantly higher proportion of IL-17 A+CD3+ T cells than the SKG model. Therapeutic blockade of IL-17 A in the C2V7 model markedly reduced both inflammatory infiltration and ectopic bone formation. Owing to its rapid onset, robustness, cost-effectiveness, and defined antigenic trigger, the C2V7 model is well-suited for probing the pathogenesis of these types of arthritis. The pronounced IL-17 A response further establishes it as a rigorous platform for evaluating related therapeutics.