Apelin-13 treats postmenopausal osteoporosis by reducing mitochondrial oxidative phosphorylation and modulating the
XiaoRong Meng1, Dandan Meng2, Chenhui Xiang3
1Department of Geriatrics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, Sichuan, China; School of Clinical Medicine, Chengdu Medical College, Chengdu, 610500, Sichuan, China.
Objective:
Postmenopausal osteoporosis (PMOP) is a prevalent metabolic bone disorder characterized by decreased bone mineral density and an increased risk of fractures. This study aims to investigate the molecular mechanisms underlying the therapeutic effects of Apelin-13 in PMOP.
Methods:
A PMOP model was established using mouse embryonic pre-osteoblast MC3T3-E1 cells treated with dexamethasone (DEX). A variety of experimental techniques-including MTT assays, Western blotting, flow cytometry, immunofluorescence staining, mitochondrial membrane potential assays, and ELISA-were employed to elucidate the potential mechanisms through which Apelin-13 exerts its therapeutic effects.
Results:
Apelin-13 significantly enhanced osteoblast activity and effectively reversed the inhibitory effects of DEX on cell proliferation. It suppressed apoptosis by modulating the expression of apoptosis-related proteins. Furthermore, Apelin-13 promoted osteogenic differentiation, upregulated osteogenic protein expression, increased alkaline phosphatase (ALP) activity, and facilitated calcium nodule formation. It also improved mitochondrial function by reducing levels of reactive oxygen species (ROS) and malondialdehyde (MDA), boosting antioxidant enzyme activity, and activating the Nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. Critically, Apelin-13 was found to regulate the OPG/RANK/RANKL/IGF-1 signaling axis, and its pro-osteogenic effects were significantly enhanced when used in combination with SPA0355.
Conclusion:
Apelin-13 exhibits promising therapeutic potential for PMOP in in vitro models by modulating key processes related to bone metabolism. It achieves this by attenuating mitochondrial oxidative phosphorylation and regulating the OPG/RANK/RANKL/IGF-1 pathway, thereby laying a foundation for future in vivo studies and clinical applications.
Insights
Apelin-13 shows potential for treating postmenopausal osteoporosis (PMOP) by enhancing osteoblast activity and improving mitochondrial function. This peptide regulates key bone metabolism pathways, offering a foundation for future clinical applications.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Medicine
Background:
- Postmenopausal osteoporosis (PMOP) is a significant health concern, characterized by reduced bone density and increased fracture risk.
- Understanding the molecular mechanisms of PMOP is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the molecular mechanisms behind the therapeutic effects of Apelin-13 in a cellular model of postmenopausal osteoporosis.
- To elucidate how Apelin-13 influences osteoblast activity, apoptosis, and bone metabolism.
Main Methods:
- Established a PMOP cellular model using dexamethasone (DEX)-treated MC3T3-E1 pre-osteoblasts.
- Utilized MTT assays, Western blotting, flow cytometry, and ELISA to analyze cell proliferation, apoptosis, and protein expression.
- Assessed mitochondrial function, reactive oxygen species (ROS) levels, and the NRF2 signaling pathway.
Main Results:
- Apelin-13 significantly boosted osteoblast proliferation and reversed DEX-induced inhibition.
- The peptide suppressed apoptosis and promoted osteogenic differentiation, evidenced by increased alkaline phosphatase (ALP) activity and calcium nodule formation.
- Apelin-13 improved mitochondrial function, reduced oxidative stress markers (ROS, MDA), and activated the NRF2 pathway.
- Apelin-13 modulated the OPG/RANK/RANKL/IGF-1 signaling axis, with enhanced effects when combined with SPA0355.
Conclusions:
- Apelin-13 demonstrates significant therapeutic potential for PMOP in vitro.
- Its mechanisms involve attenuating mitochondrial oxidative phosphorylation and regulating the OPG/RANK/RANKL/IGF-1 pathway.
- These findings support further in vivo investigation and potential clinical translation for PMOP treatment.
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