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Silibinin Can Promote Bone Regeneration of Selenium Hydrogel by Reducing the Oxidative Stress Pathway in Ovariectomized Rats

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Abstract

Osteoporosis-related bone defects are a major public health concern. Considering poor effects of a singular pharmacological treatment, many have sought combination therapies, including local treatment combined with systemic intervention. Based on recent evidence that selenium and silibinin increase bone formation and bone mineral density, it is hypothesized that systemic administration with silibinin plus local treatment with selenium may have an additive effect on bone regeneration in an OVX rat model with bone defects. To verify this hypothesis, 3-month-old ovariectomized Sprague- Dawley rats (n = 10/gp) were intraperitoneally with a dose of 50 mg/kg silibinin with selenium hydrogel scaffolds implanted into femoral metaphysis bone defect. Moreover, the MC3T3-E1 cells were co-cultured with selenium and silibinin, and observed any change of cell viability, ROS, and osteogenic activity. Experiment results show that the cell mineralization and osteogenic activity of silibinin plus selenium (SSe) group is enormously higher than the control (Con) group and selenium (Se) group, while ROS appears to be immensely reduced. Osteogenic protein expressions such as SIRT1, SOD2, RUNX-2 and OC of SSe group are significantly higher than Con group and Se group. Micro-CT and Histological analysis evaluation display that group SSe, compared with Con group and Se group, presents the strongest effect on bone regeneration, bone mineralization and higher expression of SIRT1 and SOD2. RT-qPCR analysis indicates that SSe group manifests increased SIRT1, SOD1, SOD2 and CAT than the Con group and Se group (p < 0.05). Our current study demonstrates that systemic administration with SIL plus local treatment with Se is a scheme for rapid repair of femoral condylar defects, and these effects may be achieved via reducing the oxidative stress pathway.

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Acknowledgements

This study was supported by a Grant from National Natural Science Foundation of China (82002322), Funding of “Peak” Training Program and “Panfeng” Innovation Team Project for Scientific Research of Yijishan Hospital, Wannan Medical College (Grant No. GF2019G04, PF2019005, GF2019T02 and PF2019007) and Young and Middle-aged Key Project of Wannan Medical College (WK2020ZF16).

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Authors and Affiliations

  1. Department of Orthopedics, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, No. 2, Zhe Shan Xi Road, Wuhu, 241001, Anhui, People’s Republic of China

    Zhoushan Tao, Tian-Lin Li, Min Yang & Hong-Guang Xu

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  1. Zhoushan Tao
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Correspondence to Zhoushan Tao.

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Zhoushan Tao, Tian-Lin Li, Min Yang and Hong-Guang Xu declare that they have no conflicts of interest.

Research involving Human and Animal Rights

All aspects of this research were conducted in accordance with the Chinese Guidelines for Animal Welfare and Experimental Protocols. All animal experiments were performed under the approval of the Ethics Committee of the First Affiliated Hospital of Wannan Medical College, Yijishan Hospital.

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Tao, Z., Li, TL., Yang, M. et al. Silibinin Can Promote Bone Regeneration of Selenium Hydrogel by Reducing the Oxidative Stress Pathway in Ovariectomized Rats. Calcif Tissue Int 110, 723–735 (2022). https://doi.org/10.1007/s00223-021-00936-y

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