20.500.12556/RUL-148657 Anaphase-promoting complex subunit 1 associates with bone mineral density in human osteoporotic bone Genome-wide association studies (GWAS) are one of the most common approaches to identify genetic loci that are associated with bone mineral density (BMD). Such novel genetic loci represent new potential targets for the prevention and treatment of fragility fractures. GWAS have identified hundreds of associations with BMD; however, only a few have been functionally evaluated. A locus significantly associated with femoral neck BMD at the genome-wide level is intronic SNP rs17040773 located in the intronic region of the anaphase-promoting complex subunit 1 (ANAPC1) gene (p = 1.5 × 10$^-9$). Here, we functionally evaluate the role of ANAPC1 in bone remodelling by examining the expression of ANAPC1 in human bone and muscle tissues and during the osteogenic differentiation of human primary mesenchymal stem cells (MSCs). The expression of ANAPC1 was significantly decreased 2.3-fold in bone tissues and 6.2-fold in muscle tissue from osteoporotic patients as compared to the osteoarthritic and control tissues. Next, we show that the expression of ANAPC1 changes during the osteogenic differentiation process of human MSCs. Moreover, the silencing of ANAPC1 in human osteosarcoma (HOS) cells reduced RUNX2 expression, suggesting that ANAPC1 affects osteogenic differentiation through RUNX2. Altogether, our results indicate that ANAPC1 plays a role in bone physiology and in the development of osteoporosis. anaphase-promoting complex subunit 1 osteoporosis osteogenesis osteoblast mineralisation bone formation bone mineral density kompleksna podenota 1 ki spodbuja anafazo osteogeneza mineralizacija osteoblastov tvorba kosti mineralna gostota kosti osteoporoza kosti true false true Angleški jezik Slovenski jezik Članek v reviji 2023-08-29 08:18:47 2023-08-29 08:18:51 2023-08-30 03:40:24 0000-00-00 00:00:00 2023 0 0 16 str. no. 16, art. 12895 Vol. 24 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.71-007.234 1422-0067 10.3390/ijms241612895 162450947 ijms-24-12895.pdf ijms-24-12895.pdf 1 0F99C4B0E226DEB080CF2964D3CE0B4C 3234053c212bc8297272301f544c59b8612d411fecfc1aa3c7441d68b1b08be9 edf21201-4635-11ee-a605-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=172967 https://www.mdpi.com/1422-0067/24/16/12895 1 eac1dfb1-4633-11ee-a605-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=172947 Fakulteta za farmacijo 0 0 0