20.500.12556/DiRROS-29135 Recent advances in experimental functional characterization of GWAS candidate genes in osteoporosis Osteoporosis is a multifactorial, polygenic disease characterized by reduced bone mineral density (BMD) and increased fracture risk. Genome-wide association studies (GWASs) have identified numerous loci associated with BMD and/or bone fractures, but functional characterization of these target genes is essential to understand the biological mechanisms underlying osteoporosis. This review focuses on current methodologies and key examples of successful functional studies aimed at evaluating gene function in osteoporosis research. Functional evaluation typically follows a multi-step approach. In silico analyses using omics datasets expression quantitative trait loci (eQTLs), protein quantitative trait loci (pQTLs), and DNA methylation quantitative trait loci (mQTLs) help prioritize candidate genes and predict relevant biological pathways. In vitro models, including immortalized bone-derived cell lines and primary mesenchymal stem cells (MSCs), are used to explore gene function in osteogenesis. Advanced three-dimensional culture systems provide additional physiological relevance for studying bone-related cellular processes. In situ analyses of patient-derived bone and muscle tissues offer validation in a disease-relevant context, while in vivo studies using mouse and zebrafish models enable comprehensive assessment of gene function in skeletal development and maintenance. Integration of these complementary methodologies helps translate GWAS findings into biological insights and supports the identification of novel therapeutic targets for osteoporosis. in silico analyses omics MSC human bone tissue gene expression gene knockdown in silico analize omika mezenhimske matične celice (MSC) izražanje genov v človeškem kostnem tkivu true false true Angleški jezik Slovenski jezik Neznano 2026-04-22 09:23:04 2026-04-22 09:23:05 2026-04-23 04:02:10 0000-00-00 00:00:00 2025 0 0 Nasl. z nasl. zaslona; Opis vira z dne 18. 8. 2025; str. 1-25 iss. 14, [article no.] 7237 Vol. 26 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 602.64:616.71-007.234 1422-0067 10.3390/ijms26157237 245733379 RAZ_Malavasic_Petra_2025.pdf RAZ_Malavasic_Petra_2025.pdf 1 FF506DF4B39486FFAF433FA5A633C53B 792e415f6073470c1a5c827bb168ecaba3d91444d62969f2ab6a468ea83cc020 3d2c277b-3e1c-11f1-a343-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=43532 https://www.mdpi.com/1422-0067/26/15/7237 1 1c673b80-3e1c-11f1-a343-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=43531 Univerzitetni klinični center Ljubljana 0 0 0