title: Smoke-induced signal molecules in bone marrow cells from altered low-density lipoprotein receptor-related protein 5 mice.
abstract: Mechanism underlying smoke-induced loss of bone mass is unknown. In this study, we hypothesized that protein signals induced by smoking in bone marrow may be associated with the loss of bone mass. Using a proteomics approach, we identified 38 proteins differentially expressed in bone marrow cells from low-density lipoprotein receptor-related protein 5 (Lrp5) mice exposed to cigarette smoking. Smoking effects on protein expression in bone marrow among three genotypes (Lrp5(+/+), Lrp5(G171V), and Lrp5(-/-)) varied. On the basis of the ratio of protein expression induced by smoking versus nonsmoking, smoke induced protein expression significantly in wild-type mice compared to the other two genotypes (Lrp5(G171V) and Lrp5(-/-)). These proteins include inhibitors of β-catenin and proteins associated with differentiation of osteoclasts. We observed that S100A8 and S100A9 were overexpressed in human smokers compared to nonsmokers, which confirmed the effect of smoking on the expression of two proteins in Lrp5 mice, suggesting the role of these proteins in bone remodeling. Smoke induced expression of S100A8 and S100A9 in a time-dependent fashion, which was opposite of the changes in the ratio of OPG/RANKL in bone marrow cells, suggesting that the high levels of S100A8 and S100A9 may be associated with smoke-induced bone loss by increasing bone resorption.
authors.affiliation: Genomics & Functional Proteomics Laboratories, Osteoporosis Research Center, Creighton University Medical Center, 601 N 30th Street, Suite 6730, Omaha, Nebraska 68131, USA.
authors.forename: Danjun
authors.initials: D
authors.lastname: Ma
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Bryan
authors.initials: B
authors.lastname: Hackfort
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jing
authors.initials: J
authors.lastname: Xiao
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Swanson
authors.forename: Joan
authors.initials: J
authors.lastname: Lappe
authors.forename: Peng
authors.initials: P
authors.lastname: Xiao
authors.forename: Diane
authors.initials: D
authors.lastname: Cullen
authors.forename: Mohammed
authors.initials: M
authors.lastname: Akhter
authors.forename: Robert
authors.initials: R
authors.lastname: Recker
authors.forename: Gary Guishan
authors.initials: GG
authors.lastname: Xiao
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016723:Bone Remodeling; D001862:Bone Resorption / Q000209:etiology* / Q000378:metabolism; D040501:Calgranulin A / Q000235:genetics / Q000378:metabolism; D040502:Calgranulin B / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D011859:Radiography; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects; D014026:Nicotiana / Q000009:adverse effects*
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D047908:Intracellular Signaling Peptides and Proteins; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C555483:Lrp5 protein, mouse; D053244:Osteoprotegerin; D010750:Phosphoproteins; D020543:Proteome; D053245:RANK Ligand; C086145:S100a8 protein, mouse; D012906:Smoke; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse