Skip to main content
Top
Published in: Osteoporosis International 3/2017

01-03-2017 | Original Article

Cytosolic proteome profiling of monocytes for male osteoporosis

Authors: W. Zhu, H. Shen, J-G. Zhang, L. Zhang, Y. Zeng, H-L. Huang, Y-C. Zhao, H. He, Y. Zhou, K-H. Wu, Q. Tian, L-J. Zhao, F-Y. Deng, H-W. Deng

Published in: Osteoporosis International | Issue 3/2017

Login to get access

Abstract

Summary

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.

Introduction

Osteoporosis 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.

Methods

Here, 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.

Results

Of 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.

Conclusions

The 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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Lin JT, Lane JM (2004) Osteoporosis: a review. Clin Orthop Relat Res 425:126–134CrossRef Lin JT, Lane JM (2004) Osteoporosis: a review. Clin Orthop Relat Res 425:126–134CrossRef
2.
go back to reference Deng HW et al (2002) A whole-genome linkage scan suggests several genomic regions potentially containing quantitative trait loci for osteoporosis. J Clin Endocrinol Metab 87(11):5151–5159CrossRefPubMed Deng HW et al (2002) A whole-genome linkage scan suggests several genomic regions potentially containing quantitative trait loci for osteoporosis. J Clin Endocrinol Metab 87(11):5151–5159CrossRefPubMed
3.
go back to reference Center JR et al (1999) Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 353(9156):878–882CrossRefPubMed Center JR et al (1999) Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 353(9156):878–882CrossRefPubMed
5.
go back to reference Liu YZ et al (2005) A novel pathophysiological mechanism for osteoporosis suggested by an in vivo gene expression study of circulating monocytes. J Biol Chem 280(32):29011–29016CrossRefPubMed Liu YZ et al (2005) A novel pathophysiological mechanism for osteoporosis suggested by an in vivo gene expression study of circulating monocytes. J Biol Chem 280(32):29011–29016CrossRefPubMed
7.
go back to reference Zhou Y, Deng HW, Shen H (2015) Circulating monocytes: an appropriate model for bone-related study. Osteoporos Int 26(11):2561–2572CrossRefPubMed Zhou Y, Deng HW, Shen H (2015) Circulating monocytes: an appropriate model for bone-related study. Osteoporos Int 26(11):2561–2572CrossRefPubMed
8.
go back to reference Deng FY et al (2011) Peripheral blood monocyte-expressed ANXA2 gene is involved in pathogenesis of osteoporosis in humans. Mol Cell Proteomics 10(11):M111 011700CrossRefPubMedPubMedCentral Deng FY et al (2011) Peripheral blood monocyte-expressed ANXA2 gene is involved in pathogenesis of osteoporosis in humans. Mol Cell Proteomics 10(11):M111 011700CrossRefPubMedPubMedCentral
9.
go back to reference Chen YC et al (2016) Integrative analysis of genomics and transcriptome data to identify potential functional genes of BMDs in females. J Bone Miner Res 31(5):1041–1049CrossRefPubMed Chen YC et al (2016) Integrative analysis of genomics and transcriptome data to identify potential functional genes of BMDs in females. J Bone Miner Res 31(5):1041–1049CrossRefPubMed
10.
go back to reference Farber CR (2013) Systems-level analysis of genome-wide association data. G3 (Bethesda) 3(1):119–129CrossRef Farber CR (2013) Systems-level analysis of genome-wide association data. G3 (Bethesda) 3(1):119–129CrossRef
11.
go back to reference He H et al (2014) Integrative analysis of GWASs, human protein interaction, and gene expression identified gene modules associated with BMDs. J Clin Endocrinol Metab 99(11):E2392–E2399CrossRefPubMedPubMedCentral He H et al (2014) Integrative analysis of GWASs, human protein interaction, and gene expression identified gene modules associated with BMDs. J Clin Endocrinol Metab 99(11):E2392–E2399CrossRefPubMedPubMedCentral
13.
go back to reference Chen EI et al (2006) Large scale protein profiling by combination of protein fractionation and multidimensional protein identification technology (MudPIT). Mol Cell Proteomics 5(1):53–56CrossRefPubMed Chen EI et al (2006) Large scale protein profiling by combination of protein fractionation and multidimensional protein identification technology (MudPIT). Mol Cell Proteomics 5(1):53–56CrossRefPubMed
14.
go back to reference Dreger M (2003) Proteome analysis at the level of subcellular structures. Eur J Biochem 270(4):589–599CrossRefPubMed Dreger M (2003) Proteome analysis at the level of subcellular structures. Eur J Biochem 270(4):589–599CrossRefPubMed
16.
go back to reference Kim JM et al (2007) Osteoclast precursors display dynamic metabolic shifts toward accelerated glucose metabolism at an early stage of RANKL-stimulated osteoclast differentiation. Cell Physiol Biochem 20(6):935–946CrossRefPubMed Kim JM et al (2007) Osteoclast precursors display dynamic metabolic shifts toward accelerated glucose metabolism at an early stage of RANKL-stimulated osteoclast differentiation. Cell Physiol Biochem 20(6):935–946CrossRefPubMed
17.
go back to reference Liu M et al (1996) Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes Dev 10(2):142–153CrossRefPubMed Liu M et al (1996) Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes Dev 10(2):142–153CrossRefPubMed
19.
go back to reference Hoiberg M et al (2007) Population-based reference values for bone mineral density in young men. Osteoporos Int 18(11):1507–1514CrossRefPubMed Hoiberg M et al (2007) Population-based reference values for bone mineral density in young men. Osteoporos Int 18(11):1507–1514CrossRefPubMed
20.
go back to reference Kirk RE (2013) Experimental design: procedures for the behavioral sciences (4th ed.). Sage Publications, Thousand Oaks, pp. 233–272CrossRef Kirk RE (2013) Experimental design: procedures for the behavioral sciences (4th ed.). Sage Publications, Thousand Oaks, pp. 233–272CrossRef
21.
go back to reference Guey LT et al (2011) Power in the phenotypic extremes: a simulation study of power in discovery and replication of rare variants. Genet Epidemiol 35(4):236–246PubMed Guey LT et al (2011) Power in the phenotypic extremes: a simulation study of power in discovery and replication of rare variants. Genet Epidemiol 35(4):236–246PubMed
23.
24.
go back to reference Huang da W (2009) B.T. Sherman, and R.A. Lempicki, Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37(1):1–13CrossRefPubMed Huang da W (2009) B.T. Sherman, and R.A. Lempicki, Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37(1):1–13CrossRefPubMed
25.
go back to reference Bindea G et al (2009) ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 25(8):1091–1093CrossRefPubMedPubMedCentral Bindea G et al (2009) ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 25(8):1091–1093CrossRefPubMedPubMedCentral
26.
go back to reference Szklarczyk D et al (2011) The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 39:D561–D568CrossRefPubMed Szklarczyk D et al (2011) The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 39:D561–D568CrossRefPubMed
27.
go back to reference Liu YZ et al (2015) Attenuated monocyte apoptosis, a new mechanism for osteoporosis suggested by a transcriptome-wide expression study of monocytes. PLoS One 10(2):e0116792CrossRefPubMedPubMedCentral Liu YZ et al (2015) Attenuated monocyte apoptosis, a new mechanism for osteoporosis suggested by a transcriptome-wide expression study of monocytes. PLoS One 10(2):e0116792CrossRefPubMedPubMedCentral
31.
go back to reference Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate—a practical and powerful approach to multiple testing. J Royal Stat Soc Series B—Methodol 57(1):289–300 Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate—a practical and powerful approach to multiple testing. J Royal Stat Soc Series B—Methodol 57(1):289–300
32.
go back to reference Ide R et al (1994) High glucose condition activates protein tyrosine phosphatases and deactivates insulin receptor function in insulin-sensitive rat 1 fibroblasts. Biochem Biophys Res Commun 201(1):71–77CrossRefPubMed Ide R et al (1994) High glucose condition activates protein tyrosine phosphatases and deactivates insulin receptor function in insulin-sensitive rat 1 fibroblasts. Biochem Biophys Res Commun 201(1):71–77CrossRefPubMed
33.
go back to reference Roiniotis J et al (2009) Hypoxia prolongs monocyte/macrophage survival and enhanced glycolysis is associated with their maturation under aerobic conditions. J Immunol 182(12):7974–7981CrossRefPubMed Roiniotis J et al (2009) Hypoxia prolongs monocyte/macrophage survival and enhanced glycolysis is associated with their maturation under aerobic conditions. J Immunol 182(12):7974–7981CrossRefPubMed
34.
go back to reference Zhang JG et al (2015) Integrative analysis of transcriptomic and Epigenomic data to reveal regulation patterns for BMD variation. PLoS One 10(9):e0138524CrossRefPubMedPubMedCentral Zhang JG et al (2015) Integrative analysis of transcriptomic and Epigenomic data to reveal regulation patterns for BMD variation. PLoS One 10(9):e0138524CrossRefPubMedPubMedCentral
37.
go back to reference Yam PT et al (2007) Actin-myosin network reorganization breaks symmetry at the cell rear to spontaneously initiate polarized cell motility. J Cell Biol 178(7):1207–1221CrossRefPubMedPubMedCentral Yam PT et al (2007) Actin-myosin network reorganization breaks symmetry at the cell rear to spontaneously initiate polarized cell motility. J Cell Biol 178(7):1207–1221CrossRefPubMedPubMedCentral
39.
41.
go back to reference Andersen GO et al (2002) Alpha(1)-AR-induced positive inotropic response in heart is dependent on myosin light chain phosphorylation. Am J Physiol Heart Circ Physiol 283(4):H1471–H1480CrossRefPubMed Andersen GO et al (2002) Alpha(1)-AR-induced positive inotropic response in heart is dependent on myosin light chain phosphorylation. Am J Physiol Heart Circ Physiol 283(4):H1471–H1480CrossRefPubMed
42.
go back to reference Licht AH et al (2010) Junb regulates arterial contraction capacity, cellular contractility, and motility via its target Myl9 in mice. J Clin Invest 120(7):2307–2318CrossRefPubMedPubMedCentral Licht AH et al (2010) Junb regulates arterial contraction capacity, cellular contractility, and motility via its target Myl9 in mice. J Clin Invest 120(7):2307–2318CrossRefPubMedPubMedCentral
43.
go back to reference Caron E (2003) Cellular functions of the Rap1 GTP-binding protein: a pattern emerges. J Cell Sci 116(Pt 3):435–440CrossRefPubMed Caron E (2003) Cellular functions of the Rap1 GTP-binding protein: a pattern emerges. J Cell Sci 116(Pt 3):435–440CrossRefPubMed
45.
go back to reference Tadokoro S et al (2003) Talin binding to integrin beta tails: a final common step in integrin activation. Science 302(5642):103–106CrossRefPubMed Tadokoro S et al (2003) Talin binding to integrin beta tails: a final common step in integrin activation. Science 302(5642):103–106CrossRefPubMed
Metadata
Title
Cytosolic proteome profiling of monocytes for male osteoporosis
Authors
W. Zhu
H. Shen
J-G. Zhang
L. Zhang
Y. Zeng
H-L. Huang
Y-C. Zhao
H. He
Y. Zhou
K-H. Wu
Q. Tian
L-J. Zhao
F-Y. Deng
H-W. Deng
Publication date
01-03-2017
Publisher
Springer London
Published in
Osteoporosis International / Issue 3/2017
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-016-3825-y

Other articles of this Issue 3/2017

Osteoporosis International 3/2017 Go to the issue