Carnovali Marta, Valli Roberto, Banfi Giuseppe, Porta Giovanni, Mariotti Massimo
IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy.
Centro di Medicina Genomica, Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy.
Biomedicines. 2021 Apr 6;9(4):393. doi: 10.3390/biomedicines9040393.
Inflammatory bowel disease have been linked to several health issues, including high risk of low bone mineral density. (zebrafish) is a good model to verify the effects of intestinal inflammation, since its gastrointestinal and immune systems are closely related to that of mammalians. Zebrafish is also a powerful model to study bone metabolism using the scale as the read-out model. Food strongly impacts zebrafish gut physiology, and it is well known that soybean meal induces intestinal inflammation. Adult zebrafish fed with defatted soybean meal (SBM) exhibited an intestinal inflammation evidenced by morphological alterations, inflammatory infiltrate, and increased mRNA expression of inflammatory cytokines (IL-1β, IL-6, IL-8, IL-10, TGFβ, TNF-α). The peak of acute intestinal inflammation, spanning between week 2 and 3, correlates with a transitory osteoporosis-like phenotype in the scale border. Later, a chronic inflammatory condition, associated with persistent IL-8 expression, correlates with the progression of resorption lacunae in the scale center. Both types of resorption lacunae were associated with intense osteoclastic tartrate-resistant acid phosphatase (TRAP) activity. After 3 weeks of SBM treatment, osteoclast activity decreased in the scale border but not in the center. At the same time, alkaline phosphatase (ALP) is activated in the border to repair the bone matrix. This model can contribute to elucidate in vivo the molecular mechanisms that links intestinal inflammation and bone metabolism in IBD.
炎症性肠病与多种健康问题相关,包括低骨矿物质密度的高风险。斑马鱼是验证肠道炎症影响的良好模型,因为其胃肠道和免疫系统与哺乳动物密切相关。斑马鱼也是利用鳞片作为读出模型来研究骨代谢的有力模型。食物对斑马鱼肠道生理有强烈影响,众所周知,豆粕会诱发肠道炎症。用脱脂豆粕(SBM)喂养的成年斑马鱼表现出肠道炎症,表现为形态改变、炎症浸润以及炎症细胞因子(IL-1β、IL-6、IL-8、IL-10、TGFβ、TNF-α)的mRNA表达增加。急性肠道炎症的高峰期在第2周和第3周之间,与鳞片边缘的短暂骨质疏松样表型相关。后来,与持续的IL-8表达相关的慢性炎症状态与鳞片中心吸收陷窝的进展相关。两种类型的吸收陷窝都与强烈的抗酒石酸酸性磷酸酶(TRAP)破骨细胞活性相关。SBM处理3周后,鳞片边缘的破骨细胞活性降低,但中心未降低。同时,碱性磷酸酶(ALP)在边缘被激活以修复骨基质。该模型有助于在体内阐明炎症性肠病中肠道炎症与骨代谢之间联系的分子机制。