Membrane palmitoylated protein 7 is required for osteogenesis and is linked with bone mineralisation and osteoporosis : the functional evaluation of GEFOS GWAS hit

Malavašič, Petra (author), Lojk, Jasna (author), Lovšin, Nika (author), Komadina, Radko (author), Haring, Gregor (author), Trebše, Rihard (author), Rivadeneira, Fernando (author), Karasik, David (author), Ostanek, Barbara (author), Marc, Janja (author)

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.

• Language: English
• Keywords: MPP7, adipogenesis, HOS cell lineage, human bone tissue, human muscle tissue
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy; MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 12 str.
• Numbering: Vol. 116, iss. 1, art. 128
• PID: 20.500.12556/RUL-178945
• UDC: 61:340.6
• ISSN on article: 1432-0827
• DOI: 10.1007/s00223-025-01439-w
• COBISS.SI-ID: 254301443
• Publication date in RUL: 02.02.2026

Record is a part of a journal

• Title: Calcified tissue international : and musculoskeletal research
• Shortened title: Calcif. tissue int.
• Publisher: Springer Nature
• ISSN: 1432-0827
• COBISS.SI-ID: 513641241

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: adipogeneza, celična linija HOS, človeško kostno tkivo, človeško mišično tkivo