Objective: Osteoporosis (OP) is mainly characterized by low bone mineral density (BMD) and microarchitectural
deterioration of bone tissue. We performed label-free quantitative proteomics to discover novel proteins involved in the
pathogenesis of osteoporosis.
Methods: We employed extreme sampling study design to collect subjects with low BMD (Z-score<-1.30±0.47) and high
BMD (Z-score>1.06±0.49), liquid chromatography and mass spectrometry (LC-MS) technologies to identify peripheral
blood monocyte (PBM)-expressed proteins significant for OP in Chinese elderly women (Study Sample 1) and men (Study
Sample 2), respectively.
Results: A total of 131 differentially expressed proteins (DEPs) and 200 DEPs were identified in subjects with low vs. high
BMD from the Study Samples 1 and 2, respectively. Interestingly, three DEPs (WNK1, SHTN1 and DPM1) were
significantly and consistently regulated with BMD in both genders. GO analysis showed that these DEPs were significantly
enriched in “extracellular exosome”, “protein binding” and “cell-cell adherens junction” (p < 0.05). Pathway enrichment
results showed that these DEPs were significantly enriched in “protein ubiquitination”, “ER-Phagosome pathway” and
“antigen processing” (p < 0.05). Protein-Protein Interaction (PPI) networks were constructed, pointing out key node
proteins, including HSPA8, PKM, AKT1 and ABI1. Mining data from independent -omics studies highlighted that 174
DEPs, as identified from above, were significant for OP in Caucasians as well, including WNK1 and DPM1.
Conclusion: The study identified known and novel proteins significant for OP in both genders and/or across ethnicities in both
Chinese and Caucasians. Our findings may provide clues for further research on the underlying pathogenic mechanism of OP.