Discovery and Identification of Serum Succinyl‐Proteome for Postmenopausal Women with Osteoporosis and Osteopenia

Abstract

Objective For the purpose of providing evidence for the treatment of osteoporosis and osteopenia, this study retrospectively identified succinylation‐modified sites and proteins in postmenopausal women, and bioinformatics analysis were performed. Methods From January 2016 to June 2018, a total of 30 postmenopausal women aged from 55 to 70 years old were assigned to three groups: 10 cases with osteoporosis; 10 cases with osteopenia; and 10 cases with normal bone mass. Subsequently, the serum samples were collected from all cases for succinyl‐proteome. Measures comprised label‐free quantitative analysis, succinylation enrichment techniques, the liquid chromatograph–mass spectrometer/mass spectrometer (LC‐MS/MS) methods, and bioinformatics. Results A total of 113 succinylation sites on 35 proteins were identified based on quantitative information. The variation of the different multiple folds were more than 1.2 times as a significant increase for up‐regulated and less than 1/1.2 times as a significant decrease for down‐regulated. Among the quantified succinylation sites, 66 were up‐regulated and 11 down‐regulated in the Osteopenia/Normal comparison group, 24 were up‐regulated and 44 down‐regulated in the Osteoporosis/Osteopenia comparison group, 45 were up‐regulated and 32 down‐regulated in the Osteoporosis/Normal comparison group. Among the quantified succinylation proteins, 24 were up‐regulated and 7 down‐regulated in the Osteopenia/Normal comparison group, 15 were up‐regulated and 20 down‐regulated in the Osteoporosis/Osteopenia comparison group, 20 were up‐regulated and 17 down‐regulated in the Osteoporosis/Normal comparison group. The percentage of proteins differed in immune response, signaling pathway, proteolysis, lymphocyte, leukocyte, and cell activation. Four differentially expressed proteins (apolipoprotein A‐I, apolipoprotein A‐II, hemoglobin subunit alpha, and haptoglobin) contained quantitative information; they were mediated with receptors, factors, mechanisms, that related to bone metabolism. Hemoglobin subunit alpha was screened for diagnosis of osteopenia. Conclusions The succinyl‐proteome experimental data indicated that apolipoprotein A‐I, apolipoprotein A‐II, hemoglobin subunit alpha, and haptoglobin were valuable for diagnosis and treatment in postmenopausal women with osteoporosis and osteopenia.

Keywords

• Succinylation
• Post‐Translational Modification
• Osteoporosis
• Osteopenia