20.500.12556/DiRROS-28872 Membrane palmitoylated protein 7 is required for osteogenesis and is linked with bone mineralisation and osteoporosis: the functional evaluation of GEFOS GWAS hit Genome-wide association studies have identified multiple loci associated with bone mineral density, a major determinant of osteoporotic fracture risk. At one such locus, genetic, bioinformatic, and zebrafish knockout data strongly prioritize membrane palmitoylated protein 7 (MPP7) as a candidate gene, although its precise role in bone biology remains poorly defined. MPP7 encodes a member of the p55 Stardust family of membrane-associated guanylate kinase proteins, which are key regulators of epithelial cell polarity and junctional organization. Here, we investigated the functional role of MPP7 in bone biology. We found that MPP7 expression was significantly reduced—by approximately twofold—in bone tissue from osteoporotic patients compared with osteoarthritic patients and non-osteoporotic controls. Furthermore, we generated a CRISPR/Cas9- mediated MPP7 knockout in the human osteosarcoma HOS cell line and demonstrated that MPP7 deletion impairs osteogenic differentiation and completely abrogates mineralization through downregulation of ALPL expression. Knockout cells also displayed altered morphology, suggesting that MPP7 influences osteoblast function via effects on cell polarity and adhesion. Collectively, our findings, together with zebrafish genetic evidence, indicate that MPP7 plays a critical role in osteoblast differentiation and mineralization and may contribute to osteoporosis susceptibility in humans. MPP7 adipogenesis HOS cell lineage human bone tissue human muscle tissue adipogeneza celična linija HOS človeško kostno tkivo človeško mišično tkivo true false true Angleški jezik Slovenski jezik Neznano 2026-04-10 11:04:13 2026-04-10 11:04:13 2026-04-11 03:54:48 0000-00-00 00:00:00 2025 0 0 Nasl. z nasl. zasl.; Opis vira z dne 23.10.2025; str. 1-12 iss. 1, [article no.] 128 Vol. 116 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 61:340.6 1432-0827 10.1007/s00223-025-01439-w 254301443 RAZ_Malavasic_Petra_2025.pdf RAZ_Malavasic_Petra_2025.pdf 1 FCEB5E92DB072FC7122E644C3594733A 9c2a385e5565613fc05d9a4969da1a0039130dcc60dd624360a54bfd79fee0c7 7471ba12-34bc-11f1-b941-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=43041 https://link.springer.com/article/10.1007/s00223-025-01439-w 1 425841e6-34bc-11f1-b941-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=43040 Univerzitetni klinični center Ljubljana 0 0 0