Department of Internal Medicine, Soonchunhyang University Hospital, Bucheon, Republic of Korea.
Department of Internal Medicine, National Police Hospital, Seoul, Republic of Korea.
Sci Rep. 2021 Jun 7;11(1):11923. doi: 10.1038/s41598-021-91320-1.
Ankylosing spondylitis is a male-predominant disease and previous study revealed that estrogens have an anti-inflammatory effect on the spondyloarthritis (SpA) manifestations in zymosan-induced SKG mice. This study aimed to evaluate the effect of selective estrogen receptor modulator (SERM) lasofoxifene (Laso) on disease activity of SpA. Mice were randomized into zymosan-treated, zymosan + 17β-estradiol (E2)-treated, and zymosan + Laso-treated groups. Arthritis was assessed by F-fluorodeoxyglucose (F-FDG) small-animal positron emission tomography/computed tomography and bone mineral density (BMD) was measured. Fecal samples were collected and 16S ribosomal RNA gene sequencing was used to determine gut microbiota differences. Both zymosan + E2-treated mice and zymosan + Laso-treated mice showed lower arthritis clinical scores and lower F-FDG uptake than zymosan-treated mice. BMD was significantly higher in zymosan + E2-treated mice and zymosan + Laso-treated mice than zymosan-treated mice, respectively. Fecal calprotectin levels were significantly elevated at 8 weeks after zymosan injection in zymosan-treated mice, but it was not significantly changed in zymosan + E2-treated mice and zymosan + Laso-treated mice. Gut microbiota diversity of zymosan-treated mice was significantly different from zymosan + E2-treated mice and zymosan + Laso-treated mice, respectively. There was no significant difference in gut microbiota diversity between zymosan + E2-treated mice and zymosan + Laso -treated mice. Laso inhibited joint inflammation and enhanced BMD in SKG mice, a model of SpA. Laso also affected the composition and biodiversity of gut microbiota. This study provides new knowledge regarding that selected SpA patients could benefit from SERM treatment.
强直性脊柱炎是一种男性为主的疾病，先前的研究表明雌激素对酵母聚糖诱导的 SKG 小鼠的脊柱关节炎（SpA）表现具有抗炎作用。本研究旨在评估选择性雌激素受体调节剂（SERM）拉索昔芬（Laso）对 SpA 疾病活动的影响。将小鼠随机分为酵母聚糖处理组、酵母聚糖+17β-雌二醇（E2）处理组和酵母聚糖+Laso 处理组。通过 F-氟脱氧葡萄糖（F-FDG）小动物正电子发射断层扫描/计算机断层扫描评估关节炎，并测量骨密度（BMD）。收集粪便样本，进行 16S 核糖体 RNA 基因测序，以确定肠道微生物组的差异。酵母聚糖+E2 处理组和酵母聚糖+Laso 处理组的小鼠关节炎临床评分和 F-FDG 摄取均低于酵母聚糖处理组的小鼠。酵母聚糖+E2 处理组和酵母聚糖+Laso 处理组的 BMD 分别明显高于酵母聚糖处理组的小鼠。酵母聚糖处理组小鼠在注射酵母聚糖 8 周后粪便钙卫蛋白水平显著升高，但酵母聚糖+E2 处理组和酵母聚糖+Laso 处理组的粪便钙卫蛋白水平没有明显变化。酵母聚糖处理组小鼠的肠道微生物组多样性与酵母聚糖+E2 处理组和酵母聚糖+Laso 处理组的小鼠有显著差异，而酵母聚糖+E2 处理组和酵母聚糖+Laso 处理组的小鼠之间肠道微生物组多样性没有显著差异。Laso 抑制了 SKG 小鼠的关节炎症并增强了 BMD，SKG 小鼠是 SpA 的模型。Laso 还影响了肠道微生物组的组成和生物多样性。本研究为选择性 SpA 患者可能从 SERM 治疗中获益提供了新的知识。
