Histone Deacetylases in Cartilage Homeostasis and Osteoarthritis
Histone Deacetylases in Cartilage Homeostasis and Osteoarthritis
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DOI：
10.1007/s11926-016-0602-z
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发表时间：
2016-08-01
影响因子：
5
通讯作者：
Westendorf, Jennifer J.
中科院分区：
文献类型：
--
作者：
Carpio, Lomeli R.;Westendorf, Jennifer J.
由于新的基因组和计算技术，表观基因组在复杂疾病中的参与正变得越来越清楚，研究也变得更加可行。此外，改变修饰和解释表观基因组的蛋白质活性的疗法可用于治疗癌症和神经疾病。基于前景看好的临床前结果，包括在关节炎模型中，已经提出了这些药物的许多其他用途。了解表观基因组药物对骨骼的影响是很有意义的，因为它对维持整体健康和健身很重要。在这篇综述中，我们综述了一类表观遗传修饰物，组蛋白脱乙酰酶(HDAC)如何控制正常的软骨发育和动态平衡的最新进展，以及最近旨在了解这些酶在骨关节炎(OA)中表达和活性变化的工作。我们还回顾了最近使用HDAC抑制剂的研究，并讨论了这些药物在预防骨性关节炎软骨破坏方面的潜在治疗益处和局限性。
The involvement of the epigenome in complex diseases is becoming increasingly clear and more feasible to study due to new genomic and computational technologies. Moreover, therapies altering the activities of proteins that modify and interpret the epigenome are available to treat cancers and neurological disorders. Many additional uses have been proposed for these drugs based on promising preclinical results, including in arthritis models. Understanding the effects of epigenomic drugs on the skeleton is of interest because of its importance in maintaining overall health and fitness. In this review, we summarize ongoing advancements in how one class of epigenetic modifiers, histone deacetylases (Hdacs), controls normal cartilage development and homeostasis, as well as recent work aimed at understanding the alterations in the expression and activities of these enzymes in osteoarthritis (OA). We also review recent studies utilizing Hdac inhibitors and discuss the potential therapeutic benefits and limitations of these drugs for preventing cartilage destruction in OA.