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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 (Avtor), ID Zupan, Janja (Avtor), ID Mlakar, Vid (Avtor), ID Kranjc, Tilen (Avtor), ID Marc, Janja (Avtor), ID Kern, Barbara (Avtor), ID Ostanek, Barbara (Avtor)

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Izvleček
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.

Jezik:Angleški jezik
Ključne besede:methyl-CpG binding domain proteins (MBD1), bone tissue samples, chromatin-modifying enzymes, autopsy controls, postmenopausal osteoporosis
Vrsta gradiva:Članek v reviji (dk_c)
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:FFA - Fakulteta za farmacijo
Leto izida:2018
Status objave pri reviji:Objavljeno
Verzija članka:Založnikova različica članka
Št. strani:12 str.
Številčenje:Vol. 8, art. 16215
UDK:577.218:612
ISSN pri članku:2045-2322
DOI:10.1038/s41598-018-34255-4 Povezava se odpre v novem oknu
COBISS.SI-ID:4627057 Povezava se odpre v novem oknu
Datum objave v RUL:12.03.2021
Število ogledov:294
Število prenosov:124
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Gradivo je del revije

Naslov:Scientific reports
Skrajšan naslov:Sci. rep.
Založnik:Nature Publishing Group
ISSN:2045-2322
COBISS.SI-ID:18727432 Povezava se odpre v novem oknu

Licence

Licenca:CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
Začetek licenciranja:12.03.2021

Sekundarni jezik

Jezik:Slovenski jezik
Ključne besede:oksidativni stres, homeostaza

Gradivo je financirano iz projekta

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Številka projekta:ARMR19

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Številka projekta:P3-0298
Naslov:Geni, hormonske in osebnostne spremembe pri metabolnih motnjah

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Številka projekta:J3-5511
Naslov:Mikro RNA - nove diagnostične in terapevtske tarče pri osteoporozi

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