| Title: | Membrane palmitoylated protein 7 is required for osteogenesis and is linked with bone mineralisation and osteoporosis: the functional evaluation of GEFOS GWAS hit |
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| Authors: | ID Malavašič, Petra (Author)
ID Lojk, Jasna (Author)
ID Lovšin, Nika (Author)
ID Komadina, Radko (Author)
ID Haring, Gregor (Author)
ID Trebše, Rihard (Author)
ID Rivadeneira, Fernando (Author)
ID Karasik, David (Author)
ID Ostanek, Barbara (Author)
ID Marc, Janja (Author) |
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| Files: |  PDF - Presentation file, download (2,04 MB)
MD5: FCEB5E92DB072FC7122E644C3594733A
 URL - Source URL, visit https://link.springer.com/article/10.1007/s00223-025-01439-w
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  UKC LJ - Ljubljana University Medical Centre
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| Abstract: | 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. |
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| Keywords: | MPP7, adipogenesis, HOS cell lineage, human bone tissue, human muscle tissue |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Year of publishing: | 2025 |
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| Number of pages: | str. 1-12 |
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| Numbering: | Vol. 116, iss. 1, [article no.] 128 |
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| PID: | 20.500.12556/DiRROS-28872  |
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| UDC: | 61:340.6 |
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| ISSN on article: | 1432-0827 |
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| DOI: | 10.1007/s00223-025-01439-w |
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| COBISS.SI-ID: | 254301443 |
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| Note: | Nasl. z nasl. zasl.;
Opis vira z dne 23.10.2025;
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| Publication date in DiRROS: | 10.04.2026 |
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| Views: | 130 |
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| Downloads: | 66 |
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