Y Zeng1,2, L Zhang2, W Zhu2,3, H He2, H Sheng2, Q Tian2, F-Y Deng2,4, L-S Zhang1, H-G Hu1, H-W Deng5,6. 1. College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, China. 2. Center of Bioinformatics and Genomics, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, 70112, USA. 3. College of Life Sciences, Hunan Normal University, Changsha, Hunan, 410081, China. 4. Laboratory of Proteins and Proteomics, Department of Epidemiology, Soochow University School of Public Health, Suzhou, Jiangsu, 205123, China. 5. College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, China. hdeng2@tulane.edu. 6. Center of Bioinformatics and Genomics, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, 70112, USA. hdeng2@tulane.edu.
Abstract
In this study, label-free-based quantitative subcellular proteomics integrated with network analysis highlighted several candidate genes including P4HB, ITGB1, CD36, and ACTN1 that may be involved in osteoporosis. All of them are predicted as significant membrane proteins with high confidence and enriched in bone-related biological process. The results were further verified in transcriptomic and genomic levels. INTRODUCTION: Osteoporosis is a metabolic bone disease mainly characterized by low bone mineral density (BMD). As the precursors of osteoclasts, peripheral blood monocytes (PBMs) are supported to be important candidates for identifying genes related to osteoporosis. We performed subcellular proteomics study to identify significant membrane proteins that involved in osteoporosis. METHODS: To investigate the association between monocytes, membrane proteins, and osteoporosis, we performed label-free quantitative subcellular proteomics in 59 male subjects with discordant BMD levels, with 30 high vs. 29 low BMD subjects. Subsequently, we performed integrated gene enrichment analysis, functional annotation, and pathway and network analysis based on multiple bioinformatics tools. RESULTS: A total of 1070 membrane proteins were identified and quantified. By comparing the proteins' expression level, we found 36 proteins that were differentially expressed between high and low BMD groups. Protein localization prediction supported the notion that the differentially expressed proteins, P4HB (p = 0.0021), CD36 (p = 0.0104), ACTN1 (p = 0.0381), and ITGB1 (p = 0.0385), are significant membrane proteins. Functional annotation and pathway and network analysis highlighted that P4HB, ITGB1, CD36, and ACTN1 are enriched in osteoporosis-related pathways and terms including "ECM-receptor interaction," "calcium ion binding," "leukocyte transendothelial migration," and "reduction of cytosolic calcium levels." Results from transcriptomic and genomic levels provided additional supporting evidences. CONCLUSION: Our study strongly supports the significance of the genes P4HB, ITGB1, CD36, and ACTN1 to the etiology of osteoporosis risk.
In this study, label-free-based quantitative subcellular proteomics integrated with network analysis highlighted several candidate genes including P4HB, ITGB1, CD36, and ACTN1 that may be involved in osteoporosis. All of them are predicted as significant membrane proteins with high confidence and enriched in bone-related biological process. The results were further verified in transcriptomic and genomic levels. INTRODUCTION:Osteoporosis is a metabolic bone disease mainly characterized by low bone mineral density (BMD). As the precursors of osteoclasts, peripheral blood monocytes (PBMs) are supported to be important candidates for identifying genes related to osteoporosis. We performed subcellular proteomics study to identify significant membrane proteins that involved in osteoporosis. METHODS: To investigate the association between monocytes, membrane proteins, and osteoporosis, we performed label-free quantitative subcellular proteomics in 59 male subjects with discordant BMD levels, with 30 high vs. 29 low BMD subjects. Subsequently, we performed integrated gene enrichment analysis, functional annotation, and pathway and network analysis based on multiple bioinformatics tools. RESULTS: A total of 1070 membrane proteins were identified and quantified. By comparing the proteins' expression level, we found 36 proteins that were differentially expressed between high and low BMD groups. Protein localization prediction supported the notion that the differentially expressed proteins, P4HB (p = 0.0021), CD36 (p = 0.0104), ACTN1 (p = 0.0381), and ITGB1 (p = 0.0385), are significant membrane proteins. Functional annotation and pathway and network analysis highlighted that P4HB, ITGB1, CD36, and ACTN1 are enriched in osteoporosis-related pathways and terms including "ECM-receptor interaction," "calcium ion binding," "leukocyte transendothelial migration," and "reduction of cytosolic calcium levels." Results from transcriptomic and genomic levels provided additional supporting evidences. CONCLUSION: Our study strongly supports the significance of the genes P4HB, ITGB1, CD36, and ACTN1 to the etiology of osteoporosis risk.
Authors: Frank Rauch; Somayyeh Fahiminiya; Jacek Majewski; Jian Carrot-Zhang; Sergei Boudko; Francis Glorieux; John S Mort; Hans-Peter Bächinger; Pierre Moffatt Journal: Am J Hum Genet Date: 2015-02-12 Impact factor: 11.025
Authors: Frederic Geissmann; Markus G Manz; Steffen Jung; Michael H Sieweke; Miriam Merad; Klaus Ley Journal: Science Date: 2010-02-05 Impact factor: 47.728
Authors: M Ma; D-G Huang; X Liang; L Zhang; S Cheng; B Cheng; X Qi; P Li; Y Du; L Liu; Y Zhao; M Ding; Y Wen; X Guo; F Zhang Journal: Osteoporos Int Date: 2019-04-15 Impact factor: 4.507