Smoke-Induced Signal Molecules in Bone Marrow Cells from Altered Low-Density Lipoprotein Receptor-Related Protein 5 Mice

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• 作者：Danjun Ma ; Yan Li ; Bryan Hackfort ; Yingchun Zhao ; Jing Xiao ; Patrick C. Swanson ; Joan Lappe ; Peng Xiao ; Diane Cullen ; Mohammed Akhter ; Robert Recker ; Gary Guishan Xiao
• 刊名：Journal of Proteome Research
• 出版年：2012
• 出版时间：July 6, 2012
• 年：2012
• 卷：11
• 期：7
• 页码：3548-3560
• 全文大小：651K
• 年卷期：v.11,no.7(July 6, 2012)
• ISSN：1535-3907

文摘

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鈥?鈥?/sup>) 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鈥?鈥?/sup>). These proteins include inhibitors of 尾-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.

Keywords:

Lrp5 mice; proteomics; bone marrow; Wnt/尾-catennin signaling; phosphorylation; microCT; cigarette smoke; osteogenesis; bone remodeling