Inflammatory bowel disease causes reversible suppression of osteoblast and chondrocyte function in mice
Inflammatory bowel disease causes reversible suppression of osteoblast and chondrocyte function in mice
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DOI：
10.1152/ajpgi.90696.2008
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发表时间：
2009-05-01
影响因子：
4.5
通讯作者：
McCabe, Laura R.
中科院分区：
文献类型：
--
作者：
Harris, Laura;Senagore, Patricia;McCabe, Laura R.
哈里斯·L，塞纳戈尔·P，年轻的VB，麦凯布·LR。炎症性肠病导致小鼠成骨细胞和软骨细胞功能的可逆性抑制。Am J Physiol胃肠病肝生理学296：G1020-G1029,2009。2009年3月19日首次出版；DOI：10.1152/ajpgi.90696.2008。-患有炎症性肠病的儿童患者可能会出现骨密度和身高下降。关于IBD是如何广泛影响骨骼的，人们知之甚少。为了评价IBD急性发作对骨骼生长的影响，用5%葡聚糖硫酸钠(DSS)诱导4wk龄小鼠结肠炎，观察其恢复情况。在疾病活动期和恢复早期，骨小梁密度、骨体积和骨厚度均下降。皮质骨厚度、外周和密度也降低，而内周和骨髓面积增加。这些变化似乎维持了骨骼强度，因为DSS组和对照组小鼠的惯性矩测量相似。组织学(静态和动态)、血清和RNA分析表明，成骨细胞成熟度和功能的降低是骨密度变化的原因。与某些情况下的骨质流失不同，骨髓肥胖症并没有增加。与人类的报告相似，骨骼长度减少，并与生长板厚度和软骨细胞标记物表达的减少相关。在疾病恢复期间，小鼠经历了快速增长，导致它们达到了最终的体重和骨骼长度、密度和基因表达，与健康对照组相似。活动期患者血清中肿瘤坏死因子-α升高，胰岛素样生长因子-I水平降低，随着病情恢复，血清肿瘤坏死因子-α水平恢复正常。血清肿瘤坏死因子-α(升高)和胰岛素样生长因子-I(降低)的变化与骨骼参数的变化平行，并随着恢复恢复到正常值，提示在骨骼反应中可能起作用。
Harris L, Senagore P, Young VB, McCabe LR. Inflammatory bowel disease causes reversible suppression of osteoblast and chondrocyte function in mice. Am J Physiol Gastrointest Liver Physiol 296: G1020-G1029, 2009. First published March 19, 2009; doi:10.1152/ajpgi.90696.2008.-Decreased bone density and stature can occur in pediatric patients with inflammatory bowel disease (IBD). Little is known about how IBD broadly impacts the skeleton. To evaluate the influence of an acute episode of IBD on growing bone, 4-wk-old mice were administered 5% dextran sodium sulfate (DSS) for 5 days to induce colitis and their recovery was monitored. During active disease and early recovery, trabecular bone mineral density, bone volume, and thickness were decreased. Cortical bone thickness, outer perimeter, and density were also decreased, whereas inner perimeter and marrow area were increased. These changes appear to maintain bone strength since measures of moments of inertia were similar between DSS-treated and control mice. Histological (static and dynamic), serum, and RNA analyses indicate that a decrease in osteoblast maturation and function account for changes in bone density. Unlike some conditions of bone loss, marrow adiposity did not increase. Similar to reports in humans, bone length decreased and correlated with decreases in growth plate thickness and chondrocyte marker expression. During disease recovery, mice experienced a growth spurt that led to their achieving final body weights and bone length, density, and gene expression similar to healthy controls. Increased TNF-alpha and decreased IGF-I serum levels were observed with active disease and returned to normal with recovery. Changes in serum TNF-alpha (increased) and IGF-I (decreased) paralleled changes in bone parameters and returned to normal values with recovery, suggesting a potential role in the skeletal response.