Estrogens are well known steroid hormones necessary to maintain bone health. In addition, mechanical loading, which estrogen signaling may intersect with the Wnt/-catenin pathway, is also essential for bone health. As osteocytes are known as the major mechanosensory cells embedded in mineralized bone matrix, osteocyte ER deletion mice (EROcy/Ocy) were generated by mating ER floxed mice with Dmp1-Cre mice to determine functions of ER in osteocytes. Trabecular bone mineral density of female, but not male EROcy/Ocy mice was significantly decreased. Bone formation parameters in EROcy/Ocy were significantly decreased while osteoclast parameters were unchanged. This suggests that ER in osteocytes exerts osteoprotective function by positively controlling bone formation. To identify potential targets of ER, gene array analysis of Dmp1-GFP osteocytes FACS sorted from EROcy/Ocy and control mice was performed. Expression of Mdk and Sostdc1, both known inhibitors of Wnt, were significantly increased without alteration of the mature osteocyte marker Sost or -catenin. Hindlimb unloading exacerbated the trabecular bone loss, but surprisingly cortical bone was resistant. These studies show that ER in osteocytes has osteoprotective effects in trabecular bone through regulating expression of Wnt antagonists, but conversely plays a negative role in cortical bone loss due to unloading.
Estrogen receptor α in osteocytes regulates trabecular bone formation in female mice.
Sex, Specimen part
View SamplesWe identified SLC44A5 as a gene associated with birth weight in cattle based on genome wide association studies.
The molecular effects of a polymorphism in the 5'UTR of solute carrier family 44, member 5 that is associated with birth weight in Holsteins.
Cell line
View SamplesFor the clinical treatment of chronic obstructive pulmonary disease (COPD), it is important not only to improve the airflow limitation by bronchodilation but also to suppress emphysema by controlling inflammation. In this study, we have screened for compounds that prevent elastase-induced airspace enlargement in mice from medicines already used clinically. Mepenzolate bromide, a muscarinic antagonist used to treat gastrointestinal disorders was selected. Intratracheal administration or inhalation of mepenzolate bromide decreased the severity of elastase-induced airspace enlargement, alteration of lung mechanics and respiratory dysfunction. While mepenzolate bromide showed bronchodilatory activity, most of other muscarinic antagonists tested did not improve the elastase-induced pulmonary disorders. Mepenzolate bromide suppressed elastase-induced pulmonary inflammatory responses and production of superoxide anions, and reduced the level of cigarette smoke-induced airspace enlargement and alteration of lung mechanics. Based on these results, we propose that this drug is therapeutically effective for COPD as a consequence of both its anti-inflammatory and bronchodilatory activities.
Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease.
Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Evidence that bovine forebrain embryonic zinc finger-like gene influences immune response associated with mastitis resistance.
No sample metadata fields
View SamplesTo investigate genes that might influence resistance to infection through IGF1R, we screened human breast cancer-derived OCUB-M cells transfected with expression vector encoding IGF1R using microarray analysis.
Evidence that bovine forebrain embryonic zinc finger-like gene influences immune response associated with mastitis resistance.
No sample metadata fields
View SamplesTo identify genes that influence resistance to mastitis, we scanned
Evidence that bovine forebrain embryonic zinc finger-like gene influences immune response associated with mastitis resistance.
No sample metadata fields
View SamplesDominant mutations in cardiac transcription factor genes cause human inherited congenital heart defects (CHDs), but their molecular basis is not understood. Transcription factors and Brg1/Brm-associated factor (BAF) chromatin remodeling complex interactions suggest potential mechanisms, but the role of BAF complexes in cardiogenesis is not known. Here we show that dosage of Brg1 is critical for mouse and zebrafish cardiogenesis. Disrupting the balance between Brg1 and disease-causing cardiac transcription factors, including Tbx5, Tbx20, and Nkx2-5, causes severe cardiac anomalies, revealing an essential allelic balance between Brg1 and these cardiac transcription factor genes. This suggests that relative levels of transcription factors and BAF complexes are important for heart development, which is supported by reduced occupancy of Brg1 at cardiac genes in Tbx5 haploinsufficient hearts. Our results reveal complex dosage-sensitive interdependence between transcription factors and BAF complexes, providing a potential mechanism underlying transcription factor haploinsufficiency, with implications for multigenic inheritance of CHDs.
Chromatin remodelling complex dosage modulates transcription factor function in heart development.
Specimen part
View SamplesWe generated hiPSCs from patients fibloblast with retinitis pigmentosa (RP) using retrovirus and Sendai virus vectors, which we differentiated into hiPSC derived retinal pigment epithelium using two different methods (SDIA and SFEB methods).
Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application.
Cell line
View SamplesSeries of samples studying effect of knock out Emx2 in urogenital epithelium of mouse embryos at E10.5.
Abnormal epithelial cell polarity and ectopic epidermal growth factor receptor (EGFR) expression induced in Emx2 KO embryonic gonads.
No sample metadata fields
View SamplesC. elegans exhibits thermotaxis, where most of the animals that had been cultivated at a particular temperature ranging from 15C to 25C for a few hours with a food source and then placed on a thermal gradient for an hour migrate to the cultivation temperature. In addition, animals that were previously conditioned to migrate to a certain temperature are capable of migrating to a new cultivation temperature a few hours after the cultivation temperature was shifted to the new temperature
Regulation of behavioral plasticity by systemic temperature signaling in Caenorhabditis elegans.
Specimen part
View Samples