Estrogen attenuates the spondyloarthritis manifestations of the SKG arthritis model

Background: Ankylosing spondylitis (AS) is a male-predominant disease, and radiographic evidence of damage is also more severe in males. Estrogen modulates immune-related processes such as T cell differentiation and cytokine production. This study aimed to evaluate the effect of estrogen on the disease activity of spondyloarthritis (SpA). Methods: The effects of estrogen on the development of arthritis were evaluated by performing ovariectomy and 17β-estradiol (E2) pellet implantation in zymosan-treated SKG mice. Clinical arthritis scores were measured, and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) small-animal positron emission tomography/computed tomography performed to quantify joint inflammation. The expression of inflammatory cytokines in joint tissue was measured. Results: E2-treated mice showed remarkable suppression of arthritis clinically and little infiltration of inflammatory cells in the Achilles tendon and intervertebral disc. ¹⁸F-FDG uptake was significantly lower in E2-treated mice than in sham-operated (sham) and ovariectomized mice. Expression of TNF, interferon-γ, and IL-17A was significantly reduced in E2-treated mice, whereas expression of sclerostin and Dickkopf-1 was increased in E2-treated mice compared with sham and ovariectomized mice. Conclusions: Estrogen suppressed arthritis development in SKG mice, a model of SpA. Results of this study suggest that estrogen has an anti-inflammatory effect on the spondyloarthritis manifestations of the SKG arthritis model.