Dataset Information

Gene expression profiling in monocytes and SNP association suggest the importance of the STAT1 gene for osteoporosis in both Chinese and Caucasians.

ABSTRACT: Osteoporosis is characterized mainly by low bone mineral density (BMD). Many cytokines and chemokines have been related with bone metabolism. Monocytes in the immune system are important sources of cytokines and chemokines for bone metabolism. However, no study has investigated in vivo expression of a large number of various factors simultaneously in human monocytes underlying osteoporosis. This study explored the in vivo expression pattern of general cytokines, chemokines, and their receptor genes in human monocytes and validated the significant genes by qRT-PCR and genetic association analyses. Expression profilings were performed in monocyte samples from 26 Chinese and 20 Caucasian premenopausal women with discordant BMD. Genome-wide association analysis with BMD variation was conducted in 1000 unrelated Caucasians. We selected 168 cytokines, chemokines, osteoclast-related factors, and their receptor genes for analyses. Significantly, the signal transducer and activator of transcription 1 (STAT1) gene was upregulated in the low versus the high BMD groups in both Chinese and Caucasians. We also revealed a significant association of the STAT1 gene with BMD variation in the 1000 Caucasians. Thus we conclude that the STAT1 gene is important in human circulating monocytes in the etiology of osteoporosis.

SUBMITTER: Chen XD

PROVIDER: S-EPMC3153389 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gene expression profiling in monocytes and SNP association suggest the importance of the STAT1 gene for osteoporosis in both Chinese and Caucasians.

Chen Xiang-Ding XD Xiao Peng P Lei Shu-Feng SF Liu Yao-Zhong YZ Guo Yan-Fang YF Deng Fei-Yan FY Tan Li-Jun LJ Zhu Xue-Zhen XZ Chen Fu-Rong FR Recker Robert R RR Deng Hong-Wen HW

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20100201 2

Osteoporosis is characterized mainly by low bone mineral density (BMD). Many cytokines and chemokines have been related with bone metabolism. Monocytes in the immune system are important sources of cytokines and chemokines for bone metabolism. However, no study has investigated in vivo expression of a large number of various factors simultaneously in human monocytes underlying osteoporosis. This study explored the in vivo expression pattern of general cytokines, chemokines, and their receptor ge ...[more]

PMID: 19594299

Similar Datasets

Project description:In male Caucasians with discordant hip bone mineral density (BMD), we applied the subcellular separation and proteome profiling to investigate the monocytic cytosol. Three BMD-associated proteins (ALDOA, MYH14, and Rap1B) were identified based on multiple omics evidence, and they may influence the pathogenic mechanisms of osteoporosis by regulating the activities of monocytes.IntroductionOsteoporosis is a serious public health problem, leading to significant mortality not only in aging females but also in males. Peripheral blood monocytes (PBMs) play important roles in bone metabolism by acting as precursors of osteoclasts and producing cytokines important for osteoclast development. The first cytosolic sub-proteome profiling analysis was performed in male PBMs to identify differentially expressed proteins (DEPs) that are associated with BMDs and risk of osteoporosis.MethodsHere, we conducted a comparative proteomics analysis in PBMs from Caucasian male subjects with discordant hip BMD (29 low BMD vs. 30 high BMD). To decrease the proteome complexity and expand the coverage range of the cellular proteome, we separated the PBM proteome into several subcellular compartments and focused on the cytosolic fractions, which are involved in a wide range of fundamental biochemical processes.ResultsOf the total of 3796 detected cytosolic proteins, we identified 16 significant (P < 0.05) and an additional 22 suggestive (P < 0.1) DEPs between samples with low vs. high hip BMDs. Some of the genes for DEPs, including ALDOA, MYH14, and Rap1B, showed an association with BMD in multiple omics studies (proteomic, transcriptomic, and genomic). Further bioinformatics analysis revealed the enrichment of DEPs in functional terms for monocyte proliferation, differentiation, and migration.ConclusionsThe combination strategy of subcellular separation and proteome profiling allows an in-depth and refined investigation into the composition and functions of cytosolic proteome, which may shed light on the monocyte-mediated pathogenic mechanisms of osteoporosis.

Project description:Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by biallelic autoimmune regulator (AIRE) mutations that manifests with chronic mucocutaneous candidiasis (CMC) and autoimmunity. Patients with STAT1 gain-of-function (GOF) mutations also develop CMC and autoimmunity; they exhibit increased STAT1 protein levels at baseline and STAT1 phosphorylation (pSTAT1) upon interferon (IFN)-γ stimulation relative to healthy controls. AIRE interacts functionally with a protein that directly regulates STAT1, namely protein inhibitor of activated STAT1, which inhibits STAT1 activation. Given the common clinical features between patients with AIRE and STAT1 GOF mutations, we sought to determine whether APECED patients also exhibit increased levels of STAT1 protein and phosphorylation in CD14+ monocytes. We obtained peripheral blood mononuclear cells from 8 APECED patients and 13 healthy controls and assessed the levels of STAT1 protein and STAT1 tyrosine phosphorylation at rest and following IFN-γ stimulation, as well as the levels of STAT1 mRNA. The mean STAT1 protein levels in CD14+ monocytes exhibited a ~20% significant decrease in APECED patients both at rest and after IFN-γ stimulation relative to that of healthy donors. Similarly, the mean peak value of IFN-γ-induced pSTAT1 level was ~20% significantly lower in APECED patients compared to that in healthy controls. The decrease in STAT1 and peak pSTAT1 in APECED patients was not accompanied by decreased STAT1 mRNA or anti-IFN-γ autoantibodies; instead, it correlated with the presence of autoantibodies to type I IFN and decreased AIRE-/- monocyte surface expression of IFN-γ receptor 2. Our data show that, in contrast to patients with STAT1 GOF mutations, APECED patients show a moderate but consistent and significant decrease in total STAT1 protein levels, associated with lower peak levels of pSTAT1 molecules after IFN-γ stimulation.

Project description:There is increasing need to understand patient outcomes in osteoporosis. This article discusses that fracture in osteoporosis can lead to a cycle of impairment, driven by complex psychosocial factors, having a profound impact on physical function/activity which accumulates over time. More information is required on how treatments impact physical function.IntroductionThere is increasing need to understand patient-centred outcomes in osteoporosis (OP) clinical research and management. This multi-method paper provides insight on the effect of OP on patients' physical function and everyday activity.MethodsData were collected from three sources: (1) targeted literature review on OP and physical function, conducted in MEDLINE, Embase and PsycINFO; (2) secondary thematic analysis of transcripts from patient interviews, conducted to develop a patient-reported outcome instrument. Transcripts were re-coded to focus on OP impact on daily activities and physical function for those with and without fracture history; and (3) discussions of the literature review and secondary qualitative analysis results with three clinical experts to review and interpret the importance and implications of the findings.ResultsResults suggest that OP, particularly with fracture, can have profound impacts on physical function/activity. These impacts accumulate over time through a cycle of impairment, as fracture leads to longer term detriments in physical function, including loss of muscle, activity avoidance and reduced physical capacity, which in turn leads to greater risk of fracture and potential for further physical restrictions. The cycle of impairment is complex, as other physical, psychosocial and treatment-related factors, such as comorbidities, fears and beliefs about physical activity and fracture risk influence physical function and everyday activity.ConclusionMore information on how treatments impact physical function would benefit healthcare professionals and persons with OP in making treatment decisions and improving treatment compliance/persistence, as these impacts may be more salient to patients than fracture incidence.

Dataset Information

Gene expression profiling in monocytes and SNP association suggest the importance of the STAT1 gene for osteoporosis in both Chinese and Caucasians.

Publications

Gene expression profiling in monocytes and SNP association suggest the importance of the STAT1 gene for osteoporosis in both Chinese and Caucasians.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets