Quantitative Proteomic Study of Peripheral Blood Monocytes Identified Novel Genes Involved in Osteoporosis

Abstract

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. 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. 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. 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.