Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density

The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored BMD pathways, including vesicle transport, in these cells and together with in silico bone turnover studies resulted in the prioritization of candidate genes for further investigation. Overall, the results add novel pathophysiological and molecular insight into bone health and disease.

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Bone mineral density in relation to polycystic ovary syndrome: an insight into irisin and insulin

The Scientific Journal of Al-Azhar Medical Faculty Girls ◽

10.4103/sjamf.sjamf_73_18 ◽

2019 ◽

Vol 3 (1) ◽

pp. 291

Author(s):

MahmoodD Al-Mendalawi

Keyword(s):

Bone Mineral Density ◽

Polycystic Ovary Syndrome ◽

Bone Mineral ◽

Polycystic Ovary ◽

Mineral Density ◽

Ovary Syndrome ◽

Insight Into

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Pharmacogenomics Study for Raloxifene in Postmenopausal Female with Osteoporosis

Disease Markers ◽

10.1155/2020/8855423 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Hsing-Fang Lu ◽

Po-Hsin Chou ◽

Gan-Hong Lin ◽

Wan-Hsuan Chou ◽

Shih-Tien Wang ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Genetic Variants ◽

Ion Homeostasis ◽

Iron Ion ◽

Mineral Density ◽

Increased Risk ◽

Density Response ◽

Postmenopausal Female ◽

Insight Into

Osteoporosis is characterized by decreased bone mineral density and increased risk of fracture. Raloxifene is one of the treatments of osteoporosis. However, the responses were variable among patients. Previous studies revealed that the genetic variants are involved in the regulation of treatment outcomes. To date, studies that evaluate the influence of genes across all genome on the raloxifene treatment response are still limited. In this study, a total of 41 postmenopausal osteoporosis patients under regular raloxifene treatment were included. Gene-based analysis using MAGMA was applied to investigate the genetic association with the bone mineral density response to raloxifene at the lumbar spine or femoral neck site. Results from gene-based analysis indicated several genes (GHRHR, ABHD8, and TMPRSS6) related to the responses of raloxifene. Besides, the pathways of iron ion homeostasis, osteoblast differentiation, and platelet morphogenesis were enriched which implies that these pathways might be relatively susceptible to raloxifene treatment outcome. Our study provided a novel insight into the response to raloxifene.

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A Novel Morphological Analysis of DXA-DICOM Images by Artificial Neural Networks for Estimating Bone Mineral Density in Health and Disease

Journal of Clinical Densitometry ◽

10.1016/j.jocd.2018.08.006 ◽

2019 ◽

Vol 22 (3) ◽

pp. 382-390 ◽

Cited By ~ 4

Author(s):

Ehab I. Mohamed ◽

Radwa A. Meshref ◽

Samir M. Abdel-Mageed ◽

Moustafa H. Moustafa ◽

Mohamed I. Badawi ◽

...

Keyword(s):

Bone Mineral Density ◽

Neural Networks ◽

Artificial Neural Networks ◽

Bone Mineral ◽

Morphological Analysis ◽

Mineral Density ◽

Health And Disease ◽

Artificial Neural

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Faculty Opinions recommendation of New insight into fat, muscle and bone relationship in women: determining the threshold at which body fat assumes negative relationship with bone mineral density.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733487743.793577679 ◽

2020 ◽

Author(s):

Joseph Proietto

Keyword(s):

Bone Mineral Density ◽

Body Fat ◽

Bone Mineral ◽

Negative Relationship ◽

Mineral Density ◽

Insight Into

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Serum equol, bone mineral density and biomechanical bone strength differ among four mouse strains

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2005.04.002 ◽

2005 ◽

Vol 16 (12) ◽

pp. 743-749 ◽

Cited By ~ 15

Author(s):

Wendy E. Ward ◽

Susie Kim ◽

Daphne Chan ◽

Debbie Fonseca

Keyword(s):

Bone Mineral Density ◽

Bone Strength ◽

Bone Mineral ◽

Mouse Strains ◽

Mineral Density

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Genome Wide Association Metanalysis Of Skull Bone Mineral Density Identifies Loci Relevant For Osteoporosis And Craniosynostosis

10.1101/2021.11.01.21265592 ◽

2021 ◽

Author(s):

Carolina Medina-Gomez ◽

Benjamin H. Mullin ◽

Alessandra Chesi ◽

Vid Prijatelj ◽

John P. Kemp ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Bone Growth ◽

Bone Diseases ◽

Cranial Bone ◽

Skull Bone ◽

Loss Of Function ◽

Bone Biology ◽

Mineral Density ◽

Genome Wide

Skull bone mineral density (SK-BMD) provides a suitable trait for the discovery of genes important to bone biology in general, and particularly for identifying components unique to intramembranous ossification, which cannot be captured at other skeletal sites. We assessed genetic determinants of SK-BMD in 43,800 individuals, identifying 59 genome-wide significant loci (4 novel), explaining 12.5% of its variance. Pathway and enrichment analyses of the association signals resulted in clustering within gene-sets involved in regulating the development of the skeleton; overexpressed in the musculoskeletal system; and enriched in enhancer and transcribed regions in osteoblasts. From the four novel loci (mapping to ZIC1, PRKAR1A, ATP6V1C1, GLRX3), two (ZIC1 and PRKAR1A) have previously been related to craniofacial developmental defects. Functional validation of skull development in zebrafish revealed abnormal cranial bone initiation that culminated in ectopic sutures and reduced BMD in mutated zic1 and atp6v1c1 fish and asymmetric bone growth and elevated BMD in mutated prkar1a fish. We confirmed a role of ZIC1 loss-of-function in suture patterning and discovered ATP6V1C1 gene associated with suture development. In light of the evidence presented suggesting that SK-BMD is genetically related to craniofacial abnormalities, our study opens new avenues to the understanding of the pathophysiology of craniofacial defects and towards the effective pharmacological treatment of bone diseases.

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