Balla, Bernadett and Sárvári, Miklós and Kósa, János and Kocsis-Deák, Barbara and Tóbiás, Bálint and Árvai, Kristóf and Takács, István and Podani, János and Liposits, Zsolt and Lakatos, Péter (2019) Long-term selective estrogen receptor-beta agonist treatment modulates gene expression in bone and bone marrow of ovariectomized rats. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 188. pp. 185-194. ISSN 0960-0760
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Abstract
Gonadal hormones including 17β-estradiol exert important protective functions in skeletal homeostasis. However, numerous details of ovarian hormone deficiency in the common bone marrow microenvironment have not yet been revealed and little information is available on the tissue-specific acts either, especially those via estrogen receptor beta (ERβ). The aim of the present study was therefore to examine the bone-related gene expression changes after ovariectomy (OVX) and long-term ERβ agonist diarylpropionitrile (DPN) administration. We found that OVX produced strong and widespread changes of gene expression in both femoral bone and bone marrow. In the bone out of 22 genes, 20 genes were up- and 2 were downregulated after OVX. It is noteworthy that DPN restored mRNA expression of 10 OVX-induced changes (Aldh2, Col1a1, Daam1, Fgf12, Igf1, Il6r, Nfkb1, Notch1, Notch2 and Psen1) suggesting a modulatory role of ERβ in bone physiology. In bone marrow, out of 37 categorized genes, transcription of 25 genes were up- and 12 were downregulated indicating that the marrow is highly responsive to gonadal hormones. DPN modestly affected transcription, only expression of two genes (Nfatc1 and Tgfb1) was restored by DPN action. The PI3K/Akt signaling pathway was the most affected gene cluster following the interventions in bone and bone marrow, as demonstrated by canonical variates analysis (CVA). We suggested that our results contribute to a deeper understanding of alterations in gene expression of bone and bone marrow niche elicited by ERβ and selective ERβ analogs.
| Item Type: | Article |
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| Additional Information: | Funding details: Országos Tudományos Kutatási Alapprogramok, OTKA, OTKA K115984 Funding text 1: This work was supported by the Hungarian Scientific Research Fund ( OTKA K115984 ). Funding details: K115984 Funding details: Hungarian Scientific Research Fund Funding text 1: This work was supported by the Hungarian Scientific Research Fund ( OTKA K115984 ). 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Biological Institute, Eötvös Loránd University, Budapest, Hungary Department of Neuroscience, Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary Export Date: 8 August 2019 CODEN: JSBBE Correspondence Address: Balla, B.; 1st Department of Internal Medicine, Semmelweis University, Korányi S. u. 2/a, Hungary; email: balladetti@gmail.com Chemicals/CAS: erbium, 7440-52-0; nicotinamide adenine dinucleotide, 53-84-9; phosphatidylinositol 3 kinase, 115926-52-8; protein, 67254-75-5; protein kinase B, 148640-14-6; diarylpropionitrile; Estrogen Receptor beta; Nitriles; Propionates Funding details: K115984 Funding details: Hungarian Scientific Research Fund Funding text 1: This work was supported by the Hungarian Scientific Research Fund ( OTKA K115984 ). |
| Uncontrolled Keywords: | RAT; TRANSCRIPTION; Bone; Ovariectomy; selective estrogen receptor beta agonist; |
| Subjects: | R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 10 Oct 2019 12:44 |
| Last Modified: | 10 Oct 2019 12:44 |
| URI: | http://real.mtak.hu/id/eprint/102219 |
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