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Proteomic profiling analysis of postmenopausal osteoporosis and osteopenia identifies potential proteins associated with low bone mineral density.

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 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) and Protein 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.

SUBMITTER: Huang D

PROVIDER: S-EPMC7164430 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Proteomic profiling analysis of postmenopausal osteoporosis and osteopenia identifies potential proteins associated with low bone mineral density.

Huang Dageng D Wang Yangyang Y Lv Jing J Yan Yuzhu Y Hu Ya Y Liu Cuicui C Zhang Feng F Wang Jihan J Hao Dingjun D

PeerJ 20200414

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 testing. Across all plasma samples, we quantitatively measured 1,092 proteins, ...[more]

PMID: 32328356

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Project description:BackgroundThe study investigated the associations of rs9340799:A > G (XbaI) and rs2234693:T > C (PvuII) polymorphisms in the estrogen receptor 1 gene (ESR1) with femoral neck (BMD-FN) and lumbar spine bone mineral density (BMD-LS), biochemical markers of bone turnover, calcium and phosphate levels, fracture prevalence, and a response to two types of anti-osteoporotic therapy in postmenopausal women from southern Slovakia.MethodsWe analysed 343 postmenopausal Slovak women (62.40 ± 0.46 years). The influence of rs9340799 (AA vs. AG + GG) and rs2234693 (TT vs. TC + CC) genotypes on BMD and biochemical markers was evaluated by covariance analysis adjusted for age and BMI. Binary logistic regression was used to evaluate the genotype effect on fracture prevalence. Pharmacogenetic part of the study included women who received a regular therapy of HT (17ß estradiol with progesterone; 1 mg/day for both; N = 76) or SERMs/raloxifene (60 mg/day; N = 64) during 48 months. The genotype-based BMD change was assessed by variance analysis for repeated measurements.ResultsWomen with AA genotype of rs9340799 had higher BMD-FN (+ 0.12 ± 0.57 of T-score) and BMD-LS (+ 0.17 ± 0.08 of T-score) in comparison with AG + GG. The rs2234693 polymorphism did not affect any of the monitored parameters. No effect of any ESR1 polymorphisms was found on fracture prevalence. Both types of anti-osteoporotic therapy had a positive effect on BMD improvement in FN and LS sites. Considering the effect of the ESR1 gene within the HT, the subjects with rs9340799/AA genotype showed worse response than those with GG genotype (- 0.26 ± 0.10 of BMD-FN T-score; - 0.35 ± 0.10 of BMD-LS T-score) and also with AG genotype (- 0.22 ± 0.08 of BMD-LS T-score). The rs2234693/TT genotype responded poorer in BMD-LS in comparison with TC (- 0.22 ± 0.08 of T-score) and CC (- 0.35 ± 0.09 of T-score). The effect of the ESR1 gene on raloxifene therapy was reported only in BMD-LS. Subjects with rs9340799/AA genotype had a - 0.30 ± 0.11 of T-score worse response compared to AG genotype. The rs2234693/TT genotype showed - 0.39 ± 0.11 and - 0.46 ± 0.15 lower T-scores in comparison with TC and CC genotypes, respectively.ConclusionsThe rs9340799 polymorphism may contribute to decreased BMD in postmenopausal women from southern Slovakia; however, this is not related to higher fracture prevalence. Concurrently, both polymorphisms affected a response to analysed anti-osteoporotic therapies.

Dataset Information

Proteomic profiling analysis of postmenopausal osteoporosis and osteopenia identifies potential proteins associated with low bone mineral density.

Publications

Proteomic profiling analysis of postmenopausal osteoporosis and osteopenia identifies potential proteins associated with low bone mineral density.

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