Spondyloarthritis (SpA) comprises a heterogeneous group of chronic inflammatory rheumatic diseases affecting the axial skeleton, peripheral joints, and entheses. It is uniquely characterized by the coexistence of inflammation and pathological new bone formation, ultimately leading to ankylosis. Although the precise pathogenic sequence remains incompletely defined, experimental animal models have provided essential mechanistic insights by reproducing key immunological and structural features of the disease. This narrative review synthesizes current knowledge on SpA pathophysiology derived from these models. Rodent models have demonstrated the central role of the IL-23/IL-17 axis. The HLA-B27 transgenic rat and the SKG mouse illustrate how dysregulated type 3 immunity, often amplified by intestinal dysbiosis, drives sustained entheseal inflammation. Non-HLA-B27 inflammatory models, such as proteoglycan-induced arthritis and spontaneous arthritis in DBA/1 mice, have clarified the contribution of osteogenic pathways, particularly Wnt and BMP/TGF-β signaling, in the transition from inflammation to pathological bone formation. Other models highlight the continuum between inflammatory, destructive, and anabolic processes. In transmembrane TNF transgenic mice, severe ossification occurs independently of major erosions. The TNF^ΔARE (TNFTg197) model has been instrumental in establishing a mechanistic link between impaired Wnt inhibition and ankylosis, as pharmacological blockade of Dkk-1 shifts the phenotype from erosive sacroiliitis to complete joint fusion. Together, these models have elucidated the interplay between immune activation, the microbiota, and osteogenic pathways in SpA. They remain indispensable for mechanistic research and therapeutic development and are increasingly integrated with OMICS-based approaches.
Keywords: Animal model; Endochondral ossification; Inflammatory disease; SpA.
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