Peer Review #2 of "Proteomic profiling analysis of postmenopausal osteoporosis and osteopenia identifies potential proteins associated with low bone mineral density (v0.1)"

Abstract

Postmenopausal osteoporosis (PMOP) is a major global public health concern and older women are more susceptible to experiencing fragility fractures. Our study investigated the associations between circulating proteins with bone mineral density (BMD) in postmenopausal women with or without low BMD (osteoporosis and osteopenia) using a tandem mass tag (TMT) labeling proteomic experiment and parallel reaction monitoring (PRM) testing. Across all plasma samples, we quantitatively measured 1,092 proteins, and the OP and normal control (NC) samples were differentiated by principal component analysis and a partial least squares-discrimination analysis model based on the protein profiling data. The differentially abundant proteins between the low BMD and NC samples mostly exhibited binding, molecular function regulator, transporter, and molecular transducer activity, and were involved in metabolic and cellular processes, stimulus response, biological regulation, immune system processes, and so forth. TMT analysis and RRM validation indicated that the expression of protein Lysozyme C (P61626) was negatively related to BMD, while the expression of proteins Glucosidase (A0A024R592) andProtein disulfideisomerase A5 (Q14554) was positively related to BMD values. Collectively, our results suggest that postmenopausal women with low BMD have a different proteomic profile or signature. Protein alterations may play an important role in the pathogenesis of PMOP, and they may act as novel biomarkers and targets of therapeutic agents for this disease.PeerJ reviewing PDF | ABSTRACT 14 Postmenopausal osteoporosis (PMOP) is a major global public health concern and older women 15 are more susceptible to experiencing fragility fractures. Our study investigated the associations 16 between circulating proteins with bone mineral density (BMD) in postmenopausal women with 17 or without low BMD (osteoporosis and osteopenia) using a tandem mass tag (TMT) labeling 18 proteomic experiment and parallel reaction monitoring (PRM) testing. Across all plasma samples, 19 we quantitatively measured 1,092 proteins, and the OP and normal control (NC) samples were 20 differentiated by principal component analysis and a partial least squares-discrimination analysis 21 model based on the protein profiling data. The differentially abundant proteins between the low 22 BMD and NC samples mostly exhibited binding, molecular function regulator, transporter, and 23 molecular transducer activity, and were involved in metabolic and cellular processes, stimulus 24 response, biological regulation, immune system processes, and so forth. TMT analysis and RRM 25 validation indicated that the expression of protein Lysozyme C (P61626) was negatively related 26 to BMD, while the expression of proteins Glucosidase (A0A024R592) and Protein 27 disulfideisomerase A5 (Q14554) was positively related to BMD values. Collectively, our results PeerJ reviewing PDF | Manuscript to be reviewed 28 suggest that postmenopausal women with low BMD have a different proteomic profile or 29 sig...