Abstract
Low bone mineral density (BMD) is a high-risk factor of osteoporosis (OP) and osteoporotic fracture (OF). Peripheral blood monocytes (PBM) can give birth to osteoclasts to resorb bone. Herein, we attempted to identify OP susceptible proteins in human PBM and characterize their functions in bone.Employing the label-free quantitative proteomics methodology (Easy-nLC1000 and Q-exactive) and traditional Western Blotting (WB), we discovered and validated that a key protein, i.e. Abl Interactor 1(ABI1), was significantly down-regulated in PBM in Chinese elderly men with extremely low vs. high BMD (n = 18, p < .05), as well as in OF patients vs. non-fractured (NF) subjects (n = 36, p < .05). The above down-regulation tendency was also observed in Chinese elderly women (n = 51, P < .05). For translational purpose, plasma ABI1 protein was assessed by ELISA in Chinese elderly men, which was found significantly down-regulated in OF (n = 20) vs. NF (n = 64) subjects (Mean: 0.41 vs. 1.03 ng/ml, FC = 0.39, p = .039), as well as in low (n = 32) vs. high (n = 32) BMD subjects (Mean: 0.5 vs. 1.57 ng/ml, FC = 0.32,p = .0012). ROC analyses in another independent study sample (n = 75) showed that the plasma ABI1 protein has superior performance in discriminating osteopenia and healthy subjects (AUC = 0.755, 95% CI: 0.632–0.877, p = .001). Follow-up cellular functional studies revealed that ABI1 protein significantly promoted osteoblast growth (optimal concentration 2.0 ng/ml), osteoblastic gene expression (OPN, ALP, COL1A1, p < .05) and osteoblast differentiation.ABI1 protein also significantly attenuated monocyte trans-endothelial migration and osteoclast differentiation and activity.In conclusion, ABI1 is a novel protein biomarker for OP in Chinese elderly. ABI1 protein, via promoting osteoblast growth, differentiation and activity, and attenuating monocyte trans-endothelial migration and osteoclast differentiation, influences BMD variation and fracture risk in humans. SignificancePrevious plentiful studies indicated that protein ABI1 played an essential role in the progression of several malignancies, including hepatoma, colon cancer and epithelial ovarian cancer. However, there was relatively limited understandings regarding its molecular and cellular functions relevant to bone phenotypes. Employing the label-free quantitative proteomics methodology (Easy-nLC1000 and Q-exactive) and traditional Western Blotting (WB), we discovered and validated that ABI1 was significantly down-regulated in PBM in Chinese elderly men with extremely low BMD as well as in OF patients. The down-regulation trend was consistent in plasma samples in Chinese elderly men. Follow-up cellular functional studies revealed that, on the one hand, ABI1 protein significantly promoted osteoblast growth, osteoblastic gene expression and osteoblast differentiation; on the other hand, it also significantly attenuated monocyte trans-endothelial migration and osteoclast differentiation and activity. It suggested that ABI1 is a promising biomarker with translational value.
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