20.500.12556/RUL-141292 Sex-determining region Y (SRY) attributes to gender differences in RANKL expression and incidence of osteoporosis 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. genetics metabolic bone disease osteoporosis RANKL SRY protein osteoporoza sarkom true false true Angleški jezik Slovenski jezik Članek v reviji 2022-09-28 08:00:02 2022-09-28 08:00:05 2023-03-30 16:09:03 0000-00-00 00:00:00 2019 0 0 16 str. iss. 8, art. 97 Vol. 51 Aug. 2019 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.71-007.234+616-006.3.04 2092-6413 10.1038/s12276-019-0294-3 4766321 s12276-019-0294-3.pdf s12276-019-0294-3.pdf 1 8187599342F383A69C533E3E1A4330F7 cb8c3643645cc7f0a946c05cdc90349566a4b8cbf4062691f9e36702064b094a 3a4fa550-3ef3-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=162284 https://www.nature.com/articles/s12276-019-0294-3 1 d13338de-3ef2-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=162283 Fakulteta za farmacijo 0 0 0