ArticleOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2017
A translational approach from an animal model identifies CD80 as a candidate gene for the study of bone phenotypes in postmenopausal women.
Article in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 14 citations in OpenAlex.
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- Osteoporosis: Molecular Pathology, Diagnostics, and Therapeutics.International journal of molecular sciences · 2023Review
- SOXC Transcription Factors as Diagnostic Biomarkers and Therapeutic Targets for Arthritis.International journal of molecular sciences · 2023Review
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- Comparative transcriptome analysis identifies CARM1 and DNMT3A as genes associated with osteoporosis.Scientific reports · 2020Article
- Osteoporosis: Pathophysiology and therapeutic options.EXCLI journal · 2020Review
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5 authors at 2 institutions in 1 country.
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Abstract
This study represented a translational study that first compared gene expression of B cells of BM from ovariectomized and control mice, and then analyzed some of the differentially expressed genes in women. Results showed novel genetic associations with bone phenotypes and points to the CD80 gene as relevant in postmenopausal bone loss.
introductionOsteoporosis is a multifactorial disease with a strong genetic component. However, to date, research into osteoporosis has only been able to explain a small part of its heritability. Moreover, several components of the immune system are involved in the regulation of bone metabolism. Among them, B cells occupy a prominent place.
methodsThe study consisted of two stages. In the first, gene expression in bone marrow B cells is compared between ovariectomized and SHAM control mice using microarrays. In the second, we studied the association of polymorphisms in some differentially expressed genes (DEG) in a cohort of postmenopausal women.
resultsThe present study has found 2791 DEG (false discovery rate (FDR) <5%), of which 1569 genes were upregulated (56.2%) and 1122 genes (43.8%) were downregulated. Among the most altered pathways were inflammation, interleukin signaling, B cell activation, TGF-beta signaling, oxidative stress response, and Wnt-signaling. Sixteen DEG were validated by MALDI-TOF mass spectrometry or qPCR. The translational stage of the study genotyped nine single nucleotide polymorphisms (SNPs) of DEG or related and detected association with bone mineral density (BMD) (nominal P values), while adjusting for confounders, for SNPs in the CD80, CD86, and HDAC5 genes. In the logistic regression analysis adjusted for confounders, in addition to the SNPs in the aforementioned genes, the SNPs in the MMP9 and SOX4 genes were associated with an increased risk of osteoporosis. Finally, two SNPs (in the CD80 and SOX6 genes) were associated with an increased risk of bone fragility fracture (FF). However, after Bonferroni correction for multiple testing, only the association between CD80 with BMD and risk of osteoporosis remained significant.
conclusionThese results show that the use of animal models is an appropriate method for identifying genes associated with human bone phenotypes.
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