title: Cytosolic proteome profiling of monocytes for male osteoporosis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: College of Life Sciences, Hunan Normal University, Changsha, Hunan, 410081, China.|Center for Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Center for Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA.
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.affiliation: Center for Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA.
authors.forename: J-G
authors.initials: JG
authors.lastname: Zhang
authors.affiliation: Center for Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Center for Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA.|College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Center for Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA.
authors.forename: H-L
authors.initials: HL
authors.lastname: Huang
authors.affiliation: Center for Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Zhao
authors.affiliation: Center for Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA.
authors.forename: H
authors.initials: H
authors.lastname: He
authors.affiliation: Center for Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Center for Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA.
authors.forename: K-H
authors.initials: KH
authors.lastname: Wu
authors.affiliation: Center for Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Center for Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA.
authors.forename: L-J
authors.initials: LJ
authors.lastname: Zhao
authors.affiliation: Center for Genetic Epidemiology and Genomics, Soochow University School of Public Health, Suzhou, Jiangsu, 215123, China.
authors.forename: F-Y
authors.initials: FY
authors.lastname: Deng
authors.affiliation: College of Life Sciences, Hunan Normal University, Changsha, Hunan, 410081, China. hdeng2@tulane.edu.|Center for Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA. hdeng2@tulane.edu.|College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, China. hdeng2@tulane.edu.
authors.forename: H-W
authors.initials: HW
authors.lastname: Deng
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D015519:Bone Density / Q000235:genetics / Q000502:physiology; D003600:Cytosol / Q000378:metabolism*; D005634:Fructose-Bisphosphate Aldolase / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology; D063990:Gene Ontology; D053263:Gene Regulatory Networks / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D024462:Myosin Type II / Q000096:biosynthesis / Q000235:genetics; D010024:Osteoporosis / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D020668:rap GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D005634:Fructose-Bisphosphate Aldolase; D018995:Myosin Heavy Chains; D024462:Myosin Type II; D020543:Proteome; D020668:rap GTP-Binding Proteins; C477830:MYH7b protein, human; C116753:RAP1B protein, human; C000618051:ALDOA protein, human
keywords: Cytosolic proteome; Glucose metabolism; Osteoporosis; Peripheral blood monocytes; Regulation of the actin cytoskeleton