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Epigenetic mechanisms including posttranslational histone modifications and DNA methylation are emerging as important determinants of bone homeostasis. With our case-control study we aimed to identify which chromatin-modifying enzymes could be involved in the pathology of postmenopausal osteoporosis and osteoarthritis while co-regulated by estrogens, oxidative stress and hypoxia. Gene expression of  HAT1 ,  KAT5 ,  HDAC6 ,  MBD1  and  DNMT3A  affected by oxidative stress and hypoxia in an  in vitro  qPCR screening step performed on an osteoblast cell line was analysed in trabecular bone tissue samples from 96 patients. Their expression was significantly reduced in patients with postmenopausal osteoporosis and osteoarthritis as compared to autopsy controls and significantly correlated with bone mineral density and several bone histomorphometry-derived parameters of bone quality and quantity as well as indicators of oxidative stress, RANK/RANKL/OPG system and angiogenesis. Furthermore, oxidative stress increased DNA methylation levels at the  RANKL  and  OPG  promoters while decreasing histone acetylation levels at these two genes. Our study is the first to show that higher expression of  HAT1 ,  HDAC6  and  MBD1  is associated with superior quantity as well as quality of the bone tissue having a more favourable trabecular structure.

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Epigenetic enzymes influenced by oxidative stress and hypoxia mimetic in osteoblasts are differentially expressed in patients with osteoporosis and osteoarthritis