Abstract
Numerous experiments in vitro and in vivo have shown that an appropriate increase intake of silicon can facilitate the synthesis of collagen and its stabilization and promote the differentiation and mineralization of osteoblasts. In this study, we examined whether ortho-silicic acid restrains the differentiation of osteoclast through the receptor activator of nuclear factor κB ligand (RANKL)/receptor activator of nuclear factor κB (RANK)/osteoprotegerin (OPG) signaling pathway by investigating its effect in vitro and in vivo. Bone marrow macrophage (BMM) cells were isolated and cultured with or without ortho-silicic acid, and then TRAP staining and immunofluorescence were performed to detect the differentiation of osteoclast. The RANKL-induced osteoclast marker gene and protein expression including c-Fos, nuclear factor of activated T cells cl (NFATcl), tumor necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor kappa B P50 (NF-κB P50), NF-κB P52, RANK, integrin β3, cathepsin K (CTSK), DC-STAMP, and TRAP were quantitatively detected by western blot and RT-PCR. Ovariectomized (OVX) rats were injected with ortho-silicic acid (OVX+Si group) and normal saline (OVX group), and sham-operated rats were injected with normal saline (Sham group). And micro-CT, H&E, and TRAP staining, ELISA, and western blot were performed. Ortho-silicic acid could inhibit the differentiation of osteoclast, and the marker genes and proteins were decreased. The OVX-induced bone loss could be reversed by ortho-silicic acid. Our finding demonstrated that ortho-silicic acid suppresses RANKL-induced osteoclastogenesis and has potential value as a therapeutic agent for OVX-induced bone loss.






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Data Availability
The datasets generated during the current study are available in the figshare repository. http://doi.org/https://doi.org/10.6084/m9.figshare.11671617.
Change history
07 September 2020
A Correction to this paper has been published: https://doi.org/10.1007/s12011-020-02366-7
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Funding
We gratefully acknowledge the financial support from the Department of Science and Technology of Shandong Province (2017GSF18160), Shandong Province Medical and Health Science and Technology Development Plan (2018WS328), and Qilu Hospital Youth Fund (2017QLQN05).
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Conceptualization: Wenzheng Ma; data curation: Hai Chi; formal analysis: Wenliang Wu; funding acquisition: Yunzhen Chen and Wenliang Wu; investigation: Lu Zhang; methodology: Wenzheng Ma, Fu’an Wang, and Yunhao You; project administration: Yunzhen Chen; resources: Hongming Zhou; software: Guangjun Jiao; supervision: Yunzhen Chen; validation: Hongliang Wang; writing – original draft: Wenzheng Ma; writing – review and editing: Fu’an Wang
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All animal experiments were performed in accordance with the principles and procedures of the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals and the guidelines for the animal treatment of Qilu Hospital of Shandong University (Jinan, China).
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The original version of this article unfortunately contained a mistake. The name of “Yunzhen Chen” is now corrected in the author group.
Summary Statement
Our study showed that with the presence of ortho-silicic acid, the differentiation of osteoclasts was suppressed and the OVX-induced bone loss was also inhibited and these findings may shed new light on the prevention and treatment of osteoporosis.
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Ma, W., Wang, F., You, Y. et al. Ortho-silicic Acid Inhibits RANKL-Induced Osteoclastogenesis and Reverses Ovariectomy-Induced Bone Loss In Vivo. Biol Trace Elem Res 199, 1864–1876 (2021). https://doi.org/10.1007/s12011-020-02286-6
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DOI: https://doi.org/10.1007/s12011-020-02286-6


