Estrogen attenuates the spondyloarthritis manifestations of the SKG arthritis model

Hyemin Jeong,Jaejoon Lee,In Young Kim,Hyungjin Kim,Yeong Hee Eun,Hunnyun Kim,Eun-Kyung Bae,Chan Hong Jeon,Eun-Mi Koh,Hoon-Suk Cha

doi:10.1186/s13075-017-1407-9

Abstract

BackgroundAnkylosing 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).MethodsThe 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.ResultsE2-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.ConclusionsEstrogen 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.

Highlights

Ankylosing spondylitis (AS) is a male-predominant disease, and radiographic evidence of damage is more severe in males
There were no significant differences in serum E2 between the sham and ovariectomized groups
Expression of TNFɑ, IFN-γ, and IL-17A was significantly reduced in E2-treated mice Local gene expression in the tissues of the hind paws and forepaws, which were harvested at 8 weeks after zymosan injection, was analyzed using the QuantiGene 2.0 Plex assay (Fig. 4)

Summary

Introduction

Ankylosing spondylitis (AS) is a male-predominant disease, and radiographic evidence of damage is more severe in males. This study aimed to evaluate the effect of estrogen on the disease activity of spondyloarthritis (SpA). AS is a male-predominant disease and men with this disease tend to have radiographic evidence of more severe damage [1]. Diagnosing this disease at an early stage is challenging; the classification criteria for axial spondyloarthritis (SpA) were developed by the Assessment of SpondyloArthritis international Society (ASAS) [2] and the ASAS criteria cover both patients with or without established radiographic changes in the sacroiliac joint.

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