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. © 2010 American Society for Bone and Mineral Research.
Highlights
Osteoporosis is mainly characterized by low bone mineral density (BMD)
Scientists have screened the differential gene expressions in osteoclastogenic cells using a high-throughput microarray platform.[15,16] Microarray technology has been used successfully for detection of gene expression profiles in diseases such as inflammatory breast cancer and urinary bladder cancer.[17,18] Theoretical studies supported the reliability of using a microarray platform for the quantitative characterization of gene expression.[19,20] differential gene expression profiles in circulating monocytes associated with BMD variation had not been investigated until our previous research in Caucasian females.[16]. In that study, we showed that chemokine receptor 3 (CCR3), histidine decarboxylase (HDC), and Received in original form October 24, 2008; revised form January 14, 2009; accepted July 6, 2009
There were no significant differences in age and height traits between the high and low BMD groups for both Chinese and Caucasians for expression analyses
Summary
Osteoporosis is mainly characterized by low bone mineral density (BMD). Genetic factors have important influences on BMD and osteoporosis.[1,2,3] Recent studies have shown that the immune system is strongly related to bone metabolism in terms of osteoimmunology.[4,5,6,7,8] Pathologic bone resorption was observed in immune system–related diseases such as autoimmune arthritis, periodontitis, Paget’s disease, and bone tumors.[9]Monocytes, important cells in immune system, produce a wide variety of factors such as interleukin 1 (IL-1), IL-6, tumor necrosis factor (TNF), transforming growth fator beta (TGF-b), and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3].(10) These factors are involved in bone metabolism by regulating osteoclastic differentiation. It is unknown whether other factors and mechanisms to regulate these factors are important in the ability of monocytes to affect bone metabolism To address these questions, scientists have screened the differential gene expressions in osteoclastogenic cells using a high-throughput microarray platform.[15,16] Microarray technology has been used successfully for detection of gene expression profiles in diseases such as inflammatory breast cancer and urinary bladder cancer.[17,18] Theoretical studies supported the reliability of using a microarray platform for the quantitative characterization of gene expression.[19,20] differential gene expression profiles in circulating monocytes associated with BMD variation had not been investigated until our previous research in Caucasian females.[16] In that study, we showed that chemokine receptor 3 (CCR3), histidine decarboxylase (HDC), and. We performed single-nucleotide polymorphism (SNP) association analysis with BMD to find further evidence of the identified genes at the DNA level
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