Blaschke Martina, Koepp Regine, Lenz Christof, Kruppa Jochen, Jung Klaus, Siggelkow Heide
Clinic of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, 37075 Göttingen, Germany.
Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
J Clin Transl Endocrinol. 2018 Jun 19;13:26-38. doi: 10.1016/j.jcte.2018.06.002. eCollection 2018 Sep.
Crohn's disease (CD) is associated with a higher prevalence of osteoporosis, a complication that is recognized as a significant cause of morbidity. Its pathogenesis is controversial, but the activity of CD is one contributing factor.
We stimulated SCP-1 cells (mesenchymal stem cell line) under osteogenic conditions with serum from adult patients with CD in the symptomatic phase (SP) and in remission (R) and with control sera. Concentrations of IL-6, IL-1 beta, and TNF alpha in the sera were measured. Patients were classified as normal or osteopenic/osteoporotic based on bone mineral density (BMD) T-score measurements. After 14 days in culture, protein expression and gene ontology (GO) annotation analysis was performed.
Cytokine concentrations (IL-6, IL-1 beta, TNF alpha) varied within sera groups. None of the cytokines were significantly increased in the symptomatic phase compared to remission. Protein analysis revealed 17 proteins regulated by the SP versus R phase sera of disease. A linear relationship between CDAI (Crohn's disease activity index) and normalized protein expression of APOA1 and 2, TTR, CDKAL1 and TUBB6 could be determined. Eleven proteins were found to be differentially regulated comparing osteoporosis-positive and osteoporosis-negative sera. Gene annotation and further analysis identified these genes as part of heme and erythrocyte metabolism, as well as involved in hypoxia and in endocytosis. A significant linear relationship between bone mineral density and normalized protein expression could be determined for proteins FABP3 and TTR.
Our explorative results confirm our hypothesis that factors in serum from patients with CD change the protein expression pattern of human immortalized osteoblast like cells. We suggest, that these short time changes indeed influence factors of bone metabolism.
克罗恩病（CD）与骨质疏松症的患病率较高相关，这种并发症被认为是发病的一个重要原因。其发病机制存在争议，但CD的活动是一个促成因素。
我们在成骨条件下，用处于症状期（SP）和缓解期（R）的成年CD患者的血清以及对照血清刺激SCP-1细胞（间充质干细胞系）。测量血清中白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的浓度。根据骨密度（BMD）T评分测量结果，将患者分类为正常或骨量减少/骨质疏松。培养14天后，进行蛋白质表达和基因本体（GO）注释分析。
细胞因子浓度（IL-6、IL-1β、TNF-α）在血清组中有所不同。与缓解期相比，症状期的细胞因子均未显著增加。蛋白质分析显示，有17种蛋白质受疾病的SP期与R期血清调节。可以确定克罗恩病活动指数（CDAI）与载脂蛋白A1和2、甲状腺素转运蛋白（TTR）、CDKAL1和微管蛋白β6（TUBB6）的标准化蛋白质表达之间存在线性关系。比较骨质疏松阳性和骨质疏松阴性血清发现，有11种蛋白质受到差异调节。基因注释和进一步分析确定这些基因是血红素和红细胞代谢的一部分，并且参与缺氧和内吞作用。可以确定蛋白质脂肪酸结合蛋白3（FABP3）和TTR的骨密度与标准化蛋白质表达之间存在显著的线性关系。
我们的探索性结果证实了我们的假设，即CD患者血清中的因素会改变人永生化成骨样细胞的蛋白质表达模式。我们认为，这些短期变化确实会影响骨代谢因素。
