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Linarin Protects against Cadmium-Induced Osteoporosis Via Reducing Oxidative Stress and Inflammation and Altering RANK/RANKL/OPG Pathway

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A Correction to this article was published on 14 January 2022

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Abstract

Cadmium (Cd) contamination in the environment is a major public health concern since it has been linked to osteoporosis and other bone deformities. Linarin is a flavonoid glycoside, and it can promote osteoblastogenesis. This research aimed to investigate the potential role of linarin against Cd-exposed bone deformations in mice model. In our research, male mice were randomly allocated into four groups: control, Cd-exposed, and Cd + linarin (20 and 40mg/kg/bw, respectively). Linarin prevented body weight loss, increased serum calcium (Ca) and phosphorus (P), and bone alkaline phosphatase (BAP) levels in Cd-exposed groups. Furthermore, linarin treatment at 20 and 40mg/kg/bw significantly decreased RANK and OPG, resulting in an increase in RANKL mRNA levels and protein distribution in the bone of Cd-exposed mice. In addition, the bone of Cd-exposed mice administered with linarin showed higher TRAP, NFATc1, MMP9, and RUNX2 mRNA levels and protein distribution. Linarin significantly decreased oxidative stress in Cd-exposed mice bone by decreasing MDA, a lipid peroxidation product. Moreover, linarin protects Cd-exposed mice antioxidant enzymes by increasing bone SOD, CAT, and GPx levels. Besides, linarin suppresses alterations in the inflammatory system, i.e., NF-κB p65/IKKβ, by reducing NF-κB p65, IKKβ, IL-6, and TNF-α in the bone of Cd-exposed animals. This study concluded that linarin has potential to cure osteoporosis in Cd-exposed mice by reducing oxidative stress and inflammation and modulating the RANK/RANKL/OPG pathway.

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Acknowledgements

We are really grateful to HOD of the Department of Orthopaedics for the help in technical and instrumental support.

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Funding

This study was funded by Xi’an Health and Family Planning Commission 2019 “Science and Technology +” Action Plan — Social Development Demonstration Project.

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YY, RC, and JL performed the experiments and collected data. YY, RC, and PZ drafted the manuscript. JF assisted in data collection. XW, YC, and PZ were assisted in data analysis. YY, RC, and BD assisted in the experimental design and edited the manuscript. All authors reviewed and approved the final manuscript.

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Correspondence to Bin Du.

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Yang, Y., Cheng, R., Liu, J. et al. Linarin Protects against Cadmium-Induced Osteoporosis Via Reducing Oxidative Stress and Inflammation and Altering RANK/RANKL/OPG Pathway. Biol Trace Elem Res 200, 3688–3700 (2022). https://doi.org/10.1007/s12011-021-02967-w

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