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

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

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.

• Language: English
• Keywords: genetics, metabolic bone disease, osteoporosis
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2019
• Number of pages: 16 str.
• Numbering: Vol. 51, iss. 8, art. 97
• PID: 20.500.12556/RUL-141292
• UDC: 616.71-007.234+616-006.3.04
• ISSN on article: 2092-6413
• DOI: 10.1038/s12276-019-0294-3
• COBISS.SI-ID: 4766321
• Publication date in RUL: 28.09.2022

Record is a part of a journal

• Title: Experimental and molecular medicine
• Shortened title: Exp. mol. medicine
• Publisher: Springer Nature
• ISSN: 2092-6413
• COBISS.SI-ID: 521612825

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.

Secondary language

• Language: Slovenian
• Keywords: RANKL, SRY protein, osteoporoza, sarkom