Epigenetic enzymes influenced by oxidative stress and hypoxia mimetic in osteoblasts are differentially expressed in patients with osteoporosis and osteoarthritis
Open accessAbstract
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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HAT1 is a cytoplasmic histone deacetylase whose loss is associated with early onset ageing and mitochondrial defects, and whose expression is reduced under treatment with hypoxic agents.
“HAT1 (FC = −1.12, p = 0.05) is a cytoplasmic histone deacetylase, for which loss is associated with early onset ageing and mitochondrial defects [105], and for which expression is reduced under treatment with hypoxic agents [159].”
From Early onset senescence and cognitive impairment in a murine model of repeated mTBI (2021) · cites this paper as [159]
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Early onset senescence and cognitive impairment in a murine model of repeated mTBI
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- Authors
- Vrtačnik, P., Zupan, J., Mlakar, V., Kranjc, T., Marc, J., Kern, B., & Ostanek, B.
- Affiliations
- University of Ljubljana (SI)
- Corresponding author
- Ostanek, Barbara
- Venue
- Scientific Reports
- Published
- 2018-11-01
- Volume
- 8
- Issue
- 1
- Pages
- 16215-16215
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6212423
- OpenAlex
- W2898532909
- Cited by
- 39
- References
- 33
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 7 · 2022: 4 · 2021: 11 · 2020: 7 · 2019: 4
- FWCI
- 5.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository of the University of Ljubljana (University of Ljubljana) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Javna Agencija za Raziskovalno Dejavnost RS (ARMR19, P3-0298, J3-5511)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- epigenetic enzymes, osteoporosis, osteoarthritis, postmenopausal osteoporosis, osteoblasts, oxidative stress, hypoxia, histone acetylation, histone deacetylase, DNA methylation, HAT1, KAT5, HDAC6, MBD1, DNMT3A, RANKL, OPG, bone mineral density, trabecular bone histomorphometry, angiogenesis, estrogen
- MeSH terms
- Acetylation, Hypoxia, Bone and Bones, Cell Line, Chromatin, Deferoxamine, Estradiol, Female, Gene Expression Regulation, Histones, Humans, Hydrogen Peroxide, Male, Osteoarthritis, Osteoblasts, Osteoporosis, Oxidative Stress, Epigenesis, Genetic, Epigenomics
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