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. Graphical Abstract
Funding Information
  • 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)
  • The General Program of Chongqing Natural Science Foundation (cstc2019jcyj-msxmX0299)

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