A multimodal mass spectrometry imaging approach for the study of musculoskeletal tissues
A multimodal mass spectrometry imaging approach for the study of musculoskeletal tissues
复制标题
DOI：
10.1016/j.ijms.2012.07.008
复制
发表时间：
2012-07-01
影响因子：
1.8
通讯作者：
Heeren, Ron M. A.
中科院分区：
文献类型：
--
作者：
Chughtai, Sanaullah;Chughtai, Kamila;Heeren, Ron M. A.
成像质谱将质谱的化学灵敏度和特异性与显微成像分辨率相结合。从检测到的分析物同时获得图像的能力使我们能够知道薄组织切片表面的组成。虽然这项技术是非常众所周知的，不同的应用程序已被用于不同疾病的分类，很少有人做了肌肉骨骼组织。类风湿性关节炎（RA）是一种广泛的肌肉骨骼疾病，表现出广泛的分子复杂性，这是知之甚少。在本文中，一个多模式质谱成像（MSI）的策略应用于识别和定位生物分子，如脂质，肽和蛋白质在骨骼，肌肉或皮肤从RA小鼠模型的肢体。使用高空间分辨率二次离子质谱（西姆斯）成像来成像元素和小分子分布。基质辅助激光解吸/电离（MALDI）成像补充了这些研究，揭示了磷脂和肽/蛋白质的特定分布。建立了采用“组织上消化/组织外分析”的方案用于正交肽/蛋白质鉴定。所鉴定的蛋白质包括细胞因子（如白细胞介素-18）、细胞骨架相关蛋白（肌动蛋白、微管蛋白或肌球蛋白）或参与RA中的炎症触发和自身免疫反应的金属蛋白酶家族的蛋白质。这种多模式MSI和互补蛋白质组学方法的结果导致了大量的蛋白质定位和局部相互作用，揭示了构成受RA影响的肌肉骨骼组织的不同区域的详细分子特征。多模式西姆斯成像和MALDI-MSI提供的信息揭示了肌肉骨骼疾病研究的新的和未来的可能性。(C)2012爱思唯尔有限公司版权所有。
Imaging mass spectrometry combines the chemical sensitivity and specificity of mass spectrometry with microscopic imaging resolution. The ability to simultaneously obtain images from detected analytes allows us to know the composition of the surface of a thin tissue section. Although the technology is very well known and different applications have been used like in the classification of different diseases, little has been done in musculoskeletal tissues. Rheumatoid Arthritis (RA) is a widespread musculoskeletal disease that exhibits an extensive molecular complexity that is poorly understood. In this paper a multimodal mass spectrometry imaging (MSI) strategy was applied to identify and localize biomolecules such as lipids, peptides and proteins in bone, muscle or skin from the limb of a mouse model of RA. High spatial resolution Secondary Ion Mass Spectrometry (SIMS) imaging was used to image the elemental and small molecular distributions. Matrix Assisted Laser Desorption/Ionization (MALDI) imaging complemented these studies revealing a specific distribution of phospholipids and peptides/proteins. A protocol that employs "on tissue digestion/off tissue analysis" was established for orthogonal peptide/protein identification. Among the identified proteins were cytokines (like interleukin-18), cytoskeleton related proteins (actin, tubulin or myosin) or proteins of the family of metalloproteinases that are involved in inflammation triggering and autoimmune responses in RA. The results of this multimodal MSI and complementary proteomics approach resulted in a multitude of protein localizations and local interactions that reveal detailed molecular signatures from the different regions that constitute the musculoskeletal tissues affected by RA. The information provided by multimodal SIMS imaging and MALDI-MSI, reveals new and future possibilities for the study of musculoskeletal diseases. (C) 2012 Elsevier B.V. All rights reserved.