Identification of Transcripts with Shared Roles in the Pathogenesis of Postmenopausal Osteoporosis and Cardiovascular Disease.

Autor: Reppe S; Department of Medical Biochemistry, Oslo University Hospital, 0450 Oslo, Norway.; Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, 0440 Oslo, Norway.; Department of Plastic and Reconstructive Surgery, Oslo University Hospital, 0424 Oslo, Norway., Gundersen S; Center for Bioinformatics, Department of Informatics, University of Oslo, 0313 Oslo, Norway., Sandve GK; Department of Informatics, University of Oslo, 0373 Oslo, Norway., Wang Y; NORMENT, Institute of Clinical Medicine, University of Oslo, 0450 Oslo, Norway.; Division of Mental Health and Addiction, Oslo University Hospital, 0424 Oslo, Norway.; Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA., Andreassen OA; NORMENT, Institute of Clinical Medicine, University of Oslo, 0450 Oslo, Norway.; Division of Mental Health and Addiction, Oslo University Hospital, 0424 Oslo, Norway.; Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA., Medina-Gomez C; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands., Rivadeneira F; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands., Utheim TP; Department of Medical Biochemistry, Oslo University Hospital, 0450 Oslo, Norway.; Department of Plastic and Reconstructive Surgery, Oslo University Hospital, 0424 Oslo, Norway., Hovig E; Department of Informatics, University of Oslo, 0373 Oslo, Norway.; Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0424 Oslo, Norway., Gautvik KM; Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, 0440 Oslo, Norway.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 May 20; Vol. 25 (10). Date of Electronic Publication: 2024 May 20.
DOI: 10.3390/ijms25105554
Abstrakt: Epidemiological evidence suggests existing comorbidity between postmenopausal osteoporosis (OP) and cardiovascular disease (CVD), but identification of possible shared genes is lacking. The skeletal global transcriptomes were analyzed in trans-iliac bone biopsies (n = 84) from clinically well-characterized postmenopausal women (50 to 86 years) without clinical CVD using microchips and RNA sequencing. One thousand transcripts highly correlated with areal bone mineral density (aBMD) were further analyzed using bioinformatics, and common genes overlapping with CVD and associated biological mechanisms, pathways and functions were identified. Fifty genes (45 mRNAs, 5 miRNAs) were discovered with established roles in oxidative stress, inflammatory response, endothelial function, fibrosis, dyslipidemia and osteoblastogenesis/calcification. These pleiotropic genes with possible CVD comorbidity functions were also present in transcriptomes of microvascular endothelial cells and cardiomyocytes and were differentially expressed between healthy and osteoporotic women with fragility fractures. The results were supported by a genetic pleiotropy-informed conditional False Discovery Rate approach identifying any overlap in single nucleotide polymorphisms (SNPs) within several genes encoding aBMD- and CVD-associated transcripts. The study provides transcriptional and genomic evidence for genes of importance for both BMD regulation and CVD risk in a large collection of postmenopausal bone biopsies. Most of the transcripts identified in the CVD risk categories have no previously recognized roles in OP pathogenesis and provide novel avenues for exploring the mechanistic basis for the biological association between CVD and OP.
Databáze: MEDLINE
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