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

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+/+, Lrp5G171V, 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 (Lrp5G171V 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.