Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
Inflamm Bowel Dis. 2013 Jul;19(8):1586-97. doi: 10.1097/MIB.0b013e318289e17b.
Patients with inflammatory bowel disease (IBD) are at increase risk for bone loss and fractures. Therefore, in the present study, we examined the effect of experimental IBD on bone health.
We used a murine model of colitis, Helicobacter hepaticus-infected interleukin-10-deficient animals. Molecular and histological properties of bone and intestine were examined to identify the immunopathological consequences of colitis in male and female mice.
At 6 weeks postinfection, we observed significant trabecular bone loss in male mice but surprisingly not in female mice. This was true for both distal femur and vertebral locations. In addition, H. hepaticus infection suppressed osteoblast markers only in male mice. Consistent with effects on bone health, male mice with H. hepaticus infection had more severe colitis as determined by histology and elevated levels of inflammatory cytokines in the colon. Although H. hepaticus levels in the stool appeared similar in male and female mice 1 week after infection, by 6 weeks, H. hepaticus levels were greater in male mice, indicating that H. hepaticus survival and virulence within the gastrointestinal tract could be gender dependent.
In summary, H. hepaticus-induced colitis severity and associated bone loss is gender regulated, possibly as a result of gender-specific effects on H. hepaticus colonization in the mouse gastrointestinal tract and the consequent immunopathological responses.
炎症性肠病(IBD)患者存在骨质流失和骨折风险增加的情况。因此,在本研究中,我们研究了实验性 IBD 对骨骼健康的影响。
我们使用了一种结肠炎的小鼠模型,即感染了嗜肝螺杆菌的白细胞介素-10 缺陷型动物。我们检测了骨和肠的分子和组织学特性,以确定结肠炎在雄性和雌性小鼠中的免疫病理后果。
在感染后 6 周,我们观察到雄性小鼠的骨小梁明显丢失,但令人惊讶的是,雌性小鼠没有。这在股骨远端和椎体部位都是如此。此外,嗜肝螺杆菌感染仅抑制雄性小鼠的成骨细胞标志物。与对骨骼健康的影响一致,感染嗜肝螺杆菌的雄性小鼠的结肠炎更严重,这可以通过组织学和结肠中炎症细胞因子水平的升高来确定。尽管感染后 1 周雄性和雌性小鼠的粪便中嗜肝螺杆菌水平相似,但到第 6 周时,雄性小鼠的嗜肝螺杆菌水平更高,表明嗜肝螺杆菌在胃肠道中的存活和毒力可能具有性别依赖性。
总之,嗜肝螺杆菌诱导的结肠炎严重程度和相关的骨质流失受到性别调节,这可能是由于性别特异性影响嗜肝螺杆菌在小鼠胃肠道中的定植以及随后的免疫病理反应所致。