Ankylosing enthesitis associated with up-regulated IFN-γ and IL-17 production in (BXSB × NZB) F1 male mice: a new mouse model

Abstract

We found that in contrast to (BXSB 9 NZB) F 1 female mice that spontaneously develop severe systemic lupus erythematosus (SLE), male (BXSB 9 NZB) F 1 mice are not prone to SLE, but instead develop seronegative ankylosing enthesitis in ankle/tarsal joints only when caged in groups, with the incidence reaching 83% at 7 months of age. This ankylosis is microscopically characterized by a marked proliferation of fibroblast-like cells positive for bone morphogenetic protein (BMP)-2 in association with heterotropic formation of cartilages and bones in hyperplastic entheseal tissues and subsequent fusion of tarsal bones. Elevated potentials of popliteal lymph node T cells producing interleukin (IL)-17 and interferon (IFN)-c were significantly associated with joint ankylosis, suggesting the involvement of these cytokines in effector phase mechanisms of the disease, including up-regulated BMP signaling pathways. There was no difference in serum autoantibody levels between affected and unaffected mice. Parental BXSB and NZB strains of both sexes did not develop the disease even when caged in groups, indicating that the disease develops under the control of susceptibility genes derived from both parental strains. These results indicate that (BXSB 9 NZB) F 1 male mice are a suitable model for clarifying genetic, environmental and molecular mechanisms underlying ankylosing enthesitis and related diseases.

All-Trans Retinoic Acid Improves the Effects of Bone Marrow-Derived Mesenchymal Stem Cells on the Treatment of Ankylosing Spondylitis: AnIn VitroStudy

“…Abe et al [39] found in a mouse model that upregulated IFN- γ was associated with ankylosing enthesitis. Zhao et al [40] demonstrated that IFN- γ significantly activated the promoter of the HLA-B27 gene.…”

Targeting the interleukin-23/17 axis in axial spondyloarthritis

“…Previous animal studies established the essential role of IL-23/IL-17 pathway in ankylosing enthesitis and bone remodeling [18, 19]. Animal studies also indicated that IL-23-driven inflammation can lead to new bone formation in AS [20].…”

The effect of tumor necrosis factor-blockade on new bone formation in ankylosing spondylitis

“…Unfortunately, there is no perfect animal model of spondyloarthritis. Steroid treatment or TNFa inhibition does not seem to affect new bone formation in animal models of entheseal new bone formation, although it is questionable how much this is reflective of the process in human disease [18,19]. Inflammation and erosions appear to be located at anatomically distinct locations and mechanical loading, but no T or B cells appear to driving new bone formation [17].…”