Cantley M D, Zannettino A C W, Bartold P M, Fairlie D P, Haynes D R
Discipline of Physiology, School of Medicine, University of Adelaide, SA 5005, Australia; Myeloma Research Laboratory, Cancer Theme, SAHMRI, Adelaide, SA 5000, Australia; Colgate Australian Clinical Dental Research Centre, Adelaide Dental School, University of Adelaide, SA 5005, Australia.
Discipline of Physiology, School of Medicine, University of Adelaide, SA 5005, Australia; Myeloma Research Laboratory, Cancer Theme, SAHMRI, Adelaide, SA 5000, Australia.
Bone. 2017 Feb;95:162-174. doi: 10.1016/j.bone.2016.11.028. Epub 2016 Nov 30.
Histone deacetylases (HDACs) play important roles in the epigenetic regulation of gene expression in cells and are emerging therapeutic targets for treating a wide range of diseases. HDAC inhibitors (HDACi) that act on multiple HDAC enzymes have been used clinically to treat a number of solid and hematological malignancies. HDACi are also currently being studied for their efficacy in non-malignant diseases, including pathologic bone loss, but this has necessitated a better understanding of the roles of individual HDAC enzymes, particularly the eleven zinc-containing isozymes. Selective isozyme-specific inhibitors currently being developed against class I HDACs (1, 2, 3 and 8) and class II HDACs (4, 5, 6, 7, 9 and 10) will be valuable tools for elucidating the roles played by individual HDACs in different physiological and pathological settings. Isozyme-specific HDACi promise to have greater efficacy and reduced side effects, as required for treating chronic disease over extended periods of time. This article reviews the current understanding of roles for individual HDAC isozymes and effects of HDACi on bone cells, (osteoblasts, osteoclasts and osteocytes), in relation to bone remodelling in conditions characterised by pathological bone loss, including periodontitis, rheumatoid arthritis and myeloma bone disease.
组蛋白去乙酰化酶（HDACs）在细胞基因表达的表观遗传调控中发挥着重要作用，并且正成为治疗多种疾病的新兴治疗靶点。作用于多种HDAC酶的HDAC抑制剂（HDACi）已在临床上用于治疗多种实体瘤和血液系统恶性肿瘤。目前也正在研究HDACi在非恶性疾病中的疗效，包括病理性骨质流失，但这需要更好地了解各个HDAC酶的作用，特别是11种含锌同工酶。目前正在开发的针对I类HDAC（1、2、3和8）和II类HDAC（4、5、6、7、9和10）的选择性同工酶特异性抑制剂，将成为阐明各个HDAC在不同生理和病理环境中所起作用的宝贵工具。同工酶特异性HDACi有望具有更高的疗效和更低的副作用，这是长期治疗慢性病所必需的。本文综述了目前对各个HDAC同工酶作用的认识，以及HDACi对骨细胞（成骨细胞、破骨细胞和骨细胞）的影响，这些影响与以病理性骨质流失为特征的疾病（包括牙周炎、类风湿性关节炎和骨髓瘤骨病）中的骨重塑有关。
