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从人关节软骨中提取组蛋白以研究骨关节炎中的表观遗传调控。

Histone Extraction from Human Articular Cartilage for the Study of Epigenetic Regulation in Osteoarthritis.

机构信息

Unidad de Epigenética, Grupo de Investigación en Reumatología (GIR), Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario, de A Coruña (CHUAC), Sergas, 15006 A Coruña, Spain.

Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Sevilla, Spain.

出版信息

Int J Mol Sci. 2022 Mar 20;23(6):3355. doi: 10.3390/ijms23063355.

Abstract

Osteoarthritis (OA) is a chronic disease that affects articular cartilage, causing its degeneration. Although OA is one of the most prevalent pathologies globally, there are no definitive treatments available. Recently, research has focused on elucidating the complex interplay that takes place between inflammatory processes and epigenetic regulation, showing that histone post-translational modifications (PTMs) can exert a pronounced effect on the expression of OA-related genes. OA chondrocytes enhance the production of interleukin 1β (IL-1β) and interleukin 8 (IL-8), which are epigenetically regulated. These cytokines upregulate the synthesis of matrix metalloproteinases (MMPs) and aggrecanases, which promote the extracellular matrix (ECM) destruction. This motivates the study of histone PTMs to investigate the epigenetic regulation of proinflammatory molecules, but the absence of specific protocols to extract histones from human articular cartilage has complicated this task. The lack of effective methods can be explained by the structural complexity and low cellularity of this tissue, which are responsible for the biomechanical properties that allow the movement of the joint but also complicate histone isolation. Here, we provide a histone extraction procedure specifically adapted for cryopreserved human articular cartilage that can be useful to understand epigenetic regulation in OA and accelerate the search for novel strategies.

摘要

骨关节炎(OA)是一种影响关节软骨的慢性疾病,导致其退化。尽管 OA 是全球最普遍的疾病之一,但目前尚无明确的治疗方法。最近,研究集中在阐明炎症过程和表观遗传调控之间复杂的相互作用,表明组蛋白翻译后修饰(PTMs)可以对 OA 相关基因的表达产生显著影响。OA 软骨细胞增强白细胞介素 1β(IL-1β)和白细胞介素 8(IL-8)的产生,这些细胞因子受表观遗传调控。这些细胞因子上调基质金属蛋白酶(MMPs)和聚集蛋白水解酶的合成,促进细胞外基质(ECM)的破坏。这促使人们研究组蛋白 PTMs,以研究促炎分子的表观遗传调控,但由于缺乏从人关节软骨中提取组蛋白的特定方案,这项任务变得复杂。缺乏有效的方法可以用组织的结构复杂性和低细胞性来解释,这是负责关节运动的生物力学特性的原因,但也使组蛋白分离复杂化。在这里,我们提供了一种专门适用于冷冻保存的人关节软骨的组蛋白提取程序,这对于理解 OA 中的表观遗传调控并加速寻找新的策略可能很有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1427/8955682/f1dcf9f1b121/ijms-23-03355-g001.jpg

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