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 SamplesKnockdown of AURKA by siAURKA and treatment with MLN8237 markedly inhibit the growth of GFP-SAS cells. We investigated the molecular mechanisms of siAURKA and MLN8237 using the Affymetrix GeneAtlasTM System.
No associated publication
Specimen part, Cell line, Treatment
View SamplesIn this study, sex chromosome analysis was performed in patients with oral squamous cell carcinoma (OSCC) that developed after hematopoietic stem cell transplantation from the opposite gender to examine whether OSCC originates from bone marrow (BM) stem cells. Gene expression patterns in patients with possible BM stem cell-derived OSCC were compared with those in patients with normally developed OSCC.
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Specimen part
View SamplesObjective. A variety of chemokines contribute the pathogenesis of Sjgrens syndrome (SS). However, the comprehensive analysis as for clinically potent ckemokines in SS has not been performed. In this study, focusing on CXC chemokines, we investigated the precise molecular mechanism and the clinical significance through chemokine and its receptor in the autoimmune lesions of primary SS. Methods. Gene expression profiles in the lip salivary glands (LSGs) from pSS patients and controls were analyzed using DNA microarray. Expression of chemokines and their receptor of biopsy samples of pSS pathients and controls were detected by immunofluorescence analysis. In addition, in vitro experiments using human salivary gland ductal and acinar cell lines were performed to analyze the expression of chemokines and signaling pathwaycytokines by qRT-PCR, ELISA, and Western blot analysis. Results. Gene expression profiles and immunohistochemical analysis revealed that IFN--induced CXCL9 and CXCL10 were significantly increased in LSGs of pSS patients. In vitro experiments revealed that the protein expression of CXCL10 in ductal and acinar cells was differentially regulated by IFN- or TNF- via NF-B or JAK/STAT pathway. Moreover, CXCR3 expression was detected mainly in CD68+ macrophages, CD123+ plasmacytoid dendritic cells (pDCs), and in a few CD3+ T cells. Finally, Spearman's rank analysis revealed a negative correlation between the existence of CXCR3+ cells and pathological grading in LSG tissues of pSS patients (r: -0.019, p<0.01). Conclusion. These results suggest that CXCL10/CXCR3 axis plays in a key role in autoimmune response by interaction between immune cells and target cells in the pathogenesis of pSS.
No associated publication
Sex, Specimen part
View SamplesLiver dysfunction and cirrhosis affect vasculature in several organ systems and cause impairment of organ functions, thereby increasing morbidity and mortality. If a mouse model of hepatopulmonary syndrome (HPS) could be established, greater insight into the genetic basis of the disease would be gained. Our objectives were to establish a mouse model of lung injury after common bile duct ligation (CBDL) and to investigate pulmonary pathogenesis for application in future therapeutic approaches. Balb/c mice were subjected to CBDL. Immunohistochemical analyses and real-time quantitative reverse transcriptional polymerase chain reaction were performed on pulmonary tissues. The presence of HPS markers were detected by western blot and microarray analyses. We observed extensive proliferation of CD31-positive pulmonary vascular endothelial cells 2 weeks after CBDL, and identified 11 up-regulated and 8 down-regulated proteins that were associated with angiogenesis. MMP-9 protein was highly expressed at 3 weeks after CBDL, and less expressed in lungs of the control group. Contrary to our expectation, lung pathology in our mouse model exhibited differences from that of rat models, and the mechanisms responsible for these differences are unknown. This phenomenon may be explained by contrasting processes related to TNF induction of angiogenic signaling pathways in the inflammatory phase; thus, we suggest that our mouse model can be applied to pulmonary pathological analyses in the inflammatory phase, i.e., to systemic inflammatory response syndrome, acute lung injury, and MOD syndrome.
No associated publication
Age, Specimen part
View SamplesKnockdown of Akt1 markedly inhibited the growth of GFP-SAS cells.
No associated publication
Specimen part, Cell line
View SamplesSASL1 is highly metastatic to lymph nodes. ACC2 is not metastatic. We compared gene expression on cultured cells to identify genes associated to metastatic spread patterns.
Premetastatic vasculogenesis in oral squamous cell carcinoma xenograft-draining lymph nodes.
Specimen part, Cell line
View SamplesInhibition of miR-361-3p by locked nucleic acid (LNA)/DNA antisense oligonucleotide markedly suppressed the growth of GFP-SAS cells.
MicroRNA-361-3p is a potent therapeutic target for oral squamous cell carcinoma.
Specimen part, Cell line
View SamplesThe purpose of this study was to characterize the transcriptional effects induced by subcutaneous IFN-beta-1b treatment (Betaferon, 250 g every other day) in patients with relapsing-remitting form of multiple sclerosis (MS).
Long-term genome-wide blood RNA expression profiles yield novel molecular response candidates for IFN-beta-1b treatment in relapsing remitting MS.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part
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