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Epigenetic enzymes influenced by oxidative stress and hypoxia mimetic in osteoblasts are differentially expressed in patients with osteoporosis and osteoarthritis
ID Vrtačnik, Peter (Author), ID Zupan, Janja (Author), ID Mlakar, Vid (Author), ID Kranjc, Tilen (Author), ID Marc, Janja (Author), ID Kern, Barbara (Author), ID Ostanek, Barbara (Author)

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Abstract
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.

Language:English
Keywords:methyl-CpG binding domain proteins (MBD1), bone tissue samples, chromatin-modifying enzymes, autopsy controls, postmenopausal osteoporosis
Work type:Article
Typology:1.01 - Original Scientific Article
Organization:FFA - Faculty of Pharmacy
Publication status:Published
Publication version:Version of Record
Year:2018
Number of pages:12 str.
Numbering:Vol. 8, art. 16215
PID:20.500.12556/RUL-125356 This link opens in a new window
UDC:577.218:612
ISSN on article:2045-2322
DOI:10.1038/s41598-018-34255-4 This link opens in a new window
COBISS.SI-ID:4627057 This link opens in a new window
Publication date in RUL:12.03.2021
Views:1099
Downloads:244
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Record is a part of a journal

Title:Scientific reports
Shortened title:Sci. rep.
Publisher:Nature Publishing Group
ISSN:2045-2322
COBISS.SI-ID:18727432 This link opens in a new window

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:12.03.2021

Secondary language

Language:Slovenian
Keywords:oksidativni stres, homeostaza

Projects

Funder:ARRS - Slovenian Research Agency
Project number:ARMR19

Funder:ARRS - Slovenian Research Agency
Project number:P3-0298
Name:Geni, hormonske in osebnostne spremembe pri metabolnih motnjah

Funder:ARRS - Slovenian Research Agency
Project number:J3-5511
Name:Mikro RNA - nove diagnostične in terapevtske tarče pri osteoporozi

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