[A mouse model of spondyloarthritis induced by human cartilage proteglycan]

Objective To develop a model of spondyloarthritis (SpA) in mice, and analyze their clinical manifestations, radiological and histological features, and inflammatory cytokines expression levels. Methods Fourteen-week-old female BALB/c mice were immunized by intraperitoneal injection of human cartilage proteoglycan (PG), with their peripheral joints observed and scored 3 times a week. 45 weeks after immunization, micro-computed tomography (micro-CT) was used to scan the axial and peripheral joints, and bone mineral density (BMD) and bone volume/total volume (BV/TV) of the vertebral body were analyzed. The pathological changes of the axial and peripheral joints were evaluated by HE and Safranin-Fast Green staining. The levels of tumor necrosis factor alpha (TNF-α) and interleukin 17A (IL-17A) in serum were tested by ELISA. Results 30% (6/20) of PG-induced SpA (PGISpA) mice exhibited peripheral joint swelling and joint stiffness. Micro-CT showed reduced BMD and BV/TV of the vertebral body and new bone formation in sacroiliac and spinal joints in PGISpA compared with the control. Histological staining showed inflammatory cell infiltration and abnormal proliferation of synovial cells and chondrocytes in the peripheral joints. It also observed chondrocytes proliferation in the sacroiliac joints, and increased chondrocytes and osteoblasts in the spinal joints in PGISpA mice. TNF-α and IL-17A increased at week 20 after induction and TNF-α decreased at week 45 in the serum of induced mice, while IL-17A continued to increase. Conclusion The established model of PGISpA showed similar imaging and pathological features to those of human SpA, suggesting a role of IL-17A in the pathogenesis. This model, together with its research platform, can serve as the cornerstone for SpA and model animal studies.