Department of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, 91054, Erlangen, Germany.
Institute of Radiology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, 91054, Erlangen, Germany.
Dis Model Mech. 2018 Aug 30;11(9):dmm034041. doi: 10.1242/dmm.034041.
Enthesitis is a key feature of several different rheumatic diseases. Its pathophysiology is only partially known due to the lack of access to human tissue and the shortage of reliable animal models for enthesitis. Here, we aimed to develop a model that mimics the effector phase of enthesitis and reliably leads to inflammation and new bone formation. Enthesitis was induced by local injection of monosodium urate (MSU) crystals into the metatarsal entheses of wild-type (WT) or oxidative-burst-deficient () mice. Quantitative variables of inflammation (edema, swelling) and vascularization (tissue perfusion) were assessed by magnetic resonance imaging (MRI), bone-forming activity by [F]-fluoride positron emission tomography (PET), and destruction of cortical bone and new bone formation by computed tomography (CT). Non-invasive imaging was validated by histochemical and histomorphometric analysis. While injection of MSU crystals into WT mice triggered transient mild enthesitis with no new bone formation, mice developed chronic enthesitis accompanied by massive enthesiophytes. In MRI, inflammation and blood flow in the entheses were chronically increased, while PET/CT showed osteoproliferation with enthesiophyte formation. Histochemical analyses showed chronic inflammation, increased vascularization, osteoclast differentiation and bone deposition in the affected entheseal sites. Herein we describe a fast and reliable effector model of chronic enthesitis, which is characterized by a combination of inflammation, vascularization and new bone formation. This model will help to disentangle the molecular pathways involved in the effector phase of enthesitis.
附着点炎是几种不同风湿性疾病的一个主要特征。由于无法获取人组织，以及缺乏可靠的附着点炎动物模型，其发病机制目前仅部分为人所知。在此，我们旨在开发一种可模拟附着点炎效应阶段且能可靠地导致炎症和新骨形成的模型。通过向野生型（WT）或氧化爆发缺陷型（）小鼠的跖骨附着点局部注射单钠尿酸盐（MSU）晶体来诱导附着点炎。通过磁共振成像（MRI）评估炎症（水肿、肿胀）和血管生成（组织灌注）的定量变量，通过[F]-氟代脱氧葡萄糖正电子发射断层扫描（PET）评估成骨活性，通过计算机断层扫描（CT）评估皮质骨破坏和新骨形成。非侵入性成像通过组织化学和组织形态计量学分析进行验证。虽然向 WT 小鼠注射 MSU 晶体可引发短暂的轻度附着点炎而无新骨形成，但注射到小鼠中的 MSU 晶体引发了慢性附着点炎，伴有大量附着点骨赘形成。在 MRI 中，附着点的炎症和血流呈慢性增加，而 PET/CT 显示有骨赘形成的成骨增殖。组织化学分析显示，在受影响的附着点部位存在慢性炎症、血管生成增加、破骨细胞分化和骨沉积。在此，我们描述了一种快速而可靠的慢性附着点炎效应模型，其特征是炎症、血管生成和新骨形成的结合。该模型将有助于阐明附着点炎效应阶段涉及的分子途径。
