Sex-determining region Y (SRY) attributes to gender differences in RANKL expression and incidence of osteoporosis

Kodrič, Klemen (avtor), Zupan, Janja (avtor), Kranjc, Tilen (avtor), Komadina, Radko (avtor), Mlakar, Vid (avtor), Marc, Janja (avtor), Lovšin, Nika (avtor)

Receptor activator of nuclear factor KB ligand (RANKL) plays a crucial role in bone metabolism. RANKL gene misregulation has been implicated in several bone and cancer diseases. Here, we aimed to identify novel transcription regulators of RANKL expression. We discovered that transcription factors, sex-determining region Y (SRY) and c-Myb, regulate RANKL expression. We demonstrated that c-Myb increases and male-specific SRY decreases RANKL expression through direct binding to its 5'-proximal promoter. These results are corroborated by the gene expression in human bone samples. In osteoporotic men, expression of RANKL is 17-fold higher, which correlates with the drastically reduced expression (200-fold) of Sry, suggesting that in osteoporotic men, the upregulation of RANKL is caused by a decrease of Sry. In healthy men, the expression of RANKL is 20% higher than that in healthy women. Our data suggest that gender differences in RANKL expression and bone quality could be due to the sex-specific transcription factor SRY.

• Jezik: Angleški jezik
• Ključne besede: genetics, metabolic bone disease, osteoporosis
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2019
• Št. strani: 16 str.
• Številčenje: Vol. 51, iss. 8, art. 97
• PID: 20.500.12556/RUL-141292
• UDK: 616.71-007.234+616-006.3.04
• ISSN pri članku: 2092-6413
• DOI: 10.1038/s12276-019-0294-3
• COBISS.SI-ID: 4766321
• Datum objave v RUL: 28.09.2022

Gradivo je del revije

• Naslov: Experimental and molecular medicine
• Skrajšan naslov: Exp. mol. medicine
• Založnik: Springer Nature
• ISSN: 2092-6413
• COBISS.SI-ID: 521612825

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.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: RANKL, SRY protein, osteoporoza, sarkom