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Coenzyme Q10 Protects Against Hyperlipidemia-Induced Osteoporosis by Improving Mitochondrial Function via Modulating miR-130b-3p/PGC-1α Pathway

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Abstract

In hyperlipidemia-induced osteoporosis, bone marrow mesenchymal stem cells (BMSCs) differentiate into more adipocytes than osteoblasts, leading to decreased bone formation. It is vital to elucidate the effects of hyperlipidemia on bone metabolism and seek new agents that regulate adipocyte-osteoblast lineage allocation. CoQ10, a rate-limiting coenzyme of the mitochondrial respiratory chain, has been reported to decrease oxidative stress and lipid peroxidation by functioning as a mitochondrial antioxidant. However, its effect on hyperlipidemia-induced osteoporosis remains unknown. Here, we analyzed the therapeutic mechanisms of CoQ10 on hyperlipidemia-induced osteoporosis by using high-fat diet (HFD)-treated ApoE−/− mice or oxidized low-density lipoprotein (ox-LDL)-treated BMSCs. The serum lipid levels were elevated and bone formation-related markers were decreased in HFD-treated ApoE−/− mice and ox-LDL-treated BMSCs, which could be reversed by CoQ10. Additionally, PGC-1α protein expression was decreased in HFD-treated ApoE−/− mice and ox-LDL-treated BMSCs, accompanied by mitochondrial dysfunction, decreased ATP content and overgeneration of reactive oxygen species (ROS), which could also be antagonized by CoQ10. Furthermore, PGC-1α knockdown in vitro promoted ROS generation, BMSC apoptosis, and adipogenic differentiation while attenuating osteogenic differentiation in BMSCs. Mechanistically, it suggested that the expression of PGC1-α protein was increased with miR-130b-3p inhibitor treatment in osteoporosis under hyperlipidemia conditions to improve mitochondrial function. Collectively, CoQ10 alleviates hyperlipidemia-induced osteoporosis in ApoE−/− mice and regulates adipocyte-osteoblast lineage allocation. The possible underlying mechanism may involve the improvement of mitochondrial function by modulating the miR-130b-3p/PGC-1α pathway.

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Data Availability

The data used to support the findings of this study are included within the article.

Abbreviations

ALP:

Alkaline phosphatase

BMSCs:

Bone marrow mesenchymal stem cells

CoQ10:

Coenzyme Q10

GSH:

Glutathione

HDL-C:

High-density lipoprotein

LDH:

Lactate dehydrogenase

LDL-C:

Low-density lipoprotein

MDA:

Malondialdehyde

ox-LDL:

Oxidized low-density lipoprotein

ROS:

Reactive oxidative species

RT-PCR:

Reverse transcription polymerase chain reaction

SOD:

Superoxide dismutase

T-CHO:

Total cholesterol

TG:

Triglyceride

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Funding

The work was supported in part by Grants from the National Natural Science Foundation of China (82073851), Important Science Fund of Science and Technology Bureau of Liaoning Province (2020JH2/10300056), Fund of Department of Education of Liaoning Province (LZ2019016), the open project in 2022 of Chongqing Key Laboratory for the Development and Utilization of Authentic Medicinal Materials in the Three Gorges Reservoir Area (KFKT2022004), and the General Program of Chongqing Natural Science Foundation (cstc2019jcyj-msxmX0299).

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Author notes

  1. Meng Meng and Jiaying Wang contributed equally to the manuscript and should be considered co-first authors.

Authors and Affiliations

  1. Department of Orthopaedics, First Affiliated Hospital, Dalian Medical University, No. 222, Zhongshan Road, Xigang District, Dalian, 116011, China

    Meng Meng, Jianyu Zhao & Mozhen Liu

  2. Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian, 116044, China

    Jiaying Wang, Changyuan Wang, Huihan Wang & Huijun Sun

  3. Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing, China

    Yukun Zhang

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  1. Meng Meng
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Contributions

HS and ML conceived and designed this study. MM and JW performed the major experiments, data analysis, and drafted the manuscript. CW, JZ, HW, and YZ provided technological support. All the authors read and approved this manuscript.

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Correspondence to Huijun Sun or Mozhen Liu.

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Meng Meng, Jiaying Wang, Changyuan Wang, Jianyu Zhao, Huihan Wang, Yukun Zhang, Huijun Sun, and Mozhen Liu have disclosed that they do not have any conflict of interest.

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Meng, M., Wang, J., Wang, C. et al. Coenzyme Q10 Protects Against Hyperlipidemia-Induced Osteoporosis by Improving Mitochondrial Function via Modulating miR-130b-3p/PGC-1α Pathway. Calcif Tissue Int 114, 182–199 (2024). https://doi.org/10.1007/s00223-023-01161-5

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