Attenuated monocyte apoptosis, a new mechanism for osteoporosis suggested by a transcriptome-wide expression study of monocytes.
<h4>Background</h4>Osteoporosis is caused by excessive bone resorption (by osteoclasts) over bone formation (by osteoblasts). Monocytes are important to osteoporosis by serving as progenitors of osteoclasts and produce cytokines for osteoclastogenesis.<h4>Aim</h4>To identify...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0116792 |
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| author | Yao-Zhong Liu Yu Zhou Lei Zhang Jian Li Qing Tian Ji-Gang Zhang Hong-Wen Deng |
| author_facet | Yao-Zhong Liu Yu Zhou Lei Zhang Jian Li Qing Tian Ji-Gang Zhang Hong-Wen Deng |
| author_sort | Yao-Zhong Liu |
| collection | DOAJ |
| description | <h4>Background</h4>Osteoporosis is caused by excessive bone resorption (by osteoclasts) over bone formation (by osteoblasts). Monocytes are important to osteoporosis by serving as progenitors of osteoclasts and produce cytokines for osteoclastogenesis.<h4>Aim</h4>To identify osteoporosis-related genes, we performed microarray analyses of monocytes using Affymetrix 1.0 ST arrays in 42 (including 16 pre- and 26 postmenopausal) high hip BMD (bone mineral density) vs. 31 (including 15 pre- and 16 postmenopausal) low hip BMD Caucasian female subjects. Here, high vs. low BMD is defined as belonging to top vs. bottom 30% of BMD values in population.<h4>Method</h4>Differential gene expression analysis in high vs. low BMD subjects was conducted in the total cohort as well as pre- and post-menopausal subjects. Focusing on the top differentially expressed genes identified in the total, the pre- and the postmenopausal subjects (with a p <5E-03), we performed replication of the findings in 3 independent datasets of microarray analyses of monocytes (total N = 125).<h4>Results</h4>We identified (in the 73 subjects) and successfully replicated in all the 3 independent datasets 2 genes, DAXX and PLK3. Interestingly, both genes are apoptosis induction genes and both down-regulated in the low BMD subjects. Moreover, using the top 200 genes identified in the meta-analysis across all of the 4 microarray datasets, GO term enrichment analysis identified a number of terms related to induction of apoptosis, for which the majority of component genes are also down-regulated in the low BMD subjects. Overall, our result may suggest that there might be a decreased apoptosis activity of monocytes in the low BMD subjects.<h4>Conclusion</h4>Our study for the first time suggested a decreased apoptosis rate (hence an increased survival) of monocytes, an important osteoclastogenic cell, as a novel mechanism for osteoporosis. |
| format | Article |
| id | doaj-art-aded82a4eac548768bc3e3499bc12fb8 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-aded82a4eac548768bc3e3499bc12fb82025-08-20T03:46:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01102e011679210.1371/journal.pone.0116792Attenuated monocyte apoptosis, a new mechanism for osteoporosis suggested by a transcriptome-wide expression study of monocytes.Yao-Zhong LiuYu ZhouLei ZhangJian LiQing TianJi-Gang ZhangHong-Wen Deng<h4>Background</h4>Osteoporosis is caused by excessive bone resorption (by osteoclasts) over bone formation (by osteoblasts). Monocytes are important to osteoporosis by serving as progenitors of osteoclasts and produce cytokines for osteoclastogenesis.<h4>Aim</h4>To identify osteoporosis-related genes, we performed microarray analyses of monocytes using Affymetrix 1.0 ST arrays in 42 (including 16 pre- and 26 postmenopausal) high hip BMD (bone mineral density) vs. 31 (including 15 pre- and 16 postmenopausal) low hip BMD Caucasian female subjects. Here, high vs. low BMD is defined as belonging to top vs. bottom 30% of BMD values in population.<h4>Method</h4>Differential gene expression analysis in high vs. low BMD subjects was conducted in the total cohort as well as pre- and post-menopausal subjects. Focusing on the top differentially expressed genes identified in the total, the pre- and the postmenopausal subjects (with a p <5E-03), we performed replication of the findings in 3 independent datasets of microarray analyses of monocytes (total N = 125).<h4>Results</h4>We identified (in the 73 subjects) and successfully replicated in all the 3 independent datasets 2 genes, DAXX and PLK3. Interestingly, both genes are apoptosis induction genes and both down-regulated in the low BMD subjects. Moreover, using the top 200 genes identified in the meta-analysis across all of the 4 microarray datasets, GO term enrichment analysis identified a number of terms related to induction of apoptosis, for which the majority of component genes are also down-regulated in the low BMD subjects. Overall, our result may suggest that there might be a decreased apoptosis activity of monocytes in the low BMD subjects.<h4>Conclusion</h4>Our study for the first time suggested a decreased apoptosis rate (hence an increased survival) of monocytes, an important osteoclastogenic cell, as a novel mechanism for osteoporosis.https://doi.org/10.1371/journal.pone.0116792 |
| spellingShingle | Yao-Zhong Liu Yu Zhou Lei Zhang Jian Li Qing Tian Ji-Gang Zhang Hong-Wen Deng Attenuated monocyte apoptosis, a new mechanism for osteoporosis suggested by a transcriptome-wide expression study of monocytes. PLoS ONE |
| title | Attenuated monocyte apoptosis, a new mechanism for osteoporosis suggested by a transcriptome-wide expression study of monocytes. |
| title_full | Attenuated monocyte apoptosis, a new mechanism for osteoporosis suggested by a transcriptome-wide expression study of monocytes. |
| title_fullStr | Attenuated monocyte apoptosis, a new mechanism for osteoporosis suggested by a transcriptome-wide expression study of monocytes. |
| title_full_unstemmed | Attenuated monocyte apoptosis, a new mechanism for osteoporosis suggested by a transcriptome-wide expression study of monocytes. |
| title_short | Attenuated monocyte apoptosis, a new mechanism for osteoporosis suggested by a transcriptome-wide expression study of monocytes. |
| title_sort | attenuated monocyte apoptosis a new mechanism for osteoporosis suggested by a transcriptome wide expression study of monocytes |
| url | https://doi.org/10.1371/journal.pone.0116792 |
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