A proteoglycan-induced spondyloarthritis mouse model and the therapeutic effect of CCN1 monoclonal antibody

Objective To set up a mouse model of spondyloarthritis, analyzethe clinical phenotype, radiographic and pathological features, and investigate the therapeutic effect of cysteine-rich 61 (CCN1) monoclonal antibody in spondyloarthritis mouse model. Methods Proteoglycan from bovine nasal septum was used for immunization of 14-16 week old female BALB/c mice. CCN1 monoclonal antibody 093G9 or control immunoglobulin (Ig)G were injected to the spondyloarthritis mice. The arthritis scores were analyzed by t test. Peripheral and axial joints disease development was assessed by Micro-CT and histology. Results Proteoglycan immunized mice began to develop peripheral arthritis in the 8th week. The peripheral arthritis score reached the peak (10.5±1.5) in the 11th week, with the inflammation and spur formation of the ankle and knee joint. We found infiltration of inflammation cells in intervertebral discs of the lumbar vertebrae and the caudal vertebrae. Chondrocyte proliferation couldbe seen in the meniscus of knee and lumbar intervertebral discs. In the 18th week, the intervertebral discsof thoracic vertebrae and the cervical vertebrae were also damaged. Abundant chondrocytesgathered in the intervertebral discs. The inflammation and new bone for-mation of peripheral and axial joints were more severe in control IgG group than 093G9 group. The peripheral arthritis score in the 093G9 group decreased significantly after 2 treatments, [(2.8±1.3) vs (4.2±2.1), t=2.516, P<0.05]. The difference in arthritis scores between the two groups was the most significant after 8 treatments, [(2.0±2.0) vs (5.3±2.0), t=4.082, P<0.01]. Conclusion The mouse model of spondyloarthritissimulates human spondylo-arthritis, including inflammation and new bone formation in peripheral and axial joints. CCN1 monoclonal antibody can improve the inflammation and new bone formation inspondyloarthritis mouse model. Key words: Spondylitis; Disease; Models, animal; Inflammation; Osteogenesis