Ortho-silicic Acid Inhibits RANKL-Induced Osteoclastogenesis and Reverses Ovariectomy-Induced Bone Loss In Vivo
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Ortho-silicic Acid Inhibits RANKL-Induced Osteoclastogenesis and Reverses Ovariectomy-Induced Bone Loss In Vivo Wenzheng Ma 1 & Fu’an Wang 1 & Yunhao You 1 & Wenliang Wu 1 & Hai Chi 2 & Guangjun Jiao 1 & Lu Zhang 1 & Hongming Zhou 3 & Hongliang Wang 1 & Yunzheng Chen 1 Received: 10 March 2020 / Accepted: 10 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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 OVXinduced bone loss could be reversed by ortho-silicic acid. Our finding demonstrated that ortho-silicic acid suppresses RANKLinduced osteoclastogenesis and has potential value as a therapeutic agent for OVX-induced bone loss. Keywords Osteoclast . Ortho-silicic acid . Osteoporosis . Ovariectomy . RANKL
Introduction Osteoporosis is a systemic skeletal disease characterized by decreased bone mass and degeneration of bone microstructure, resulting in increased bone brittleness and a tendency to Wenzheng Ma, Fu’an Wang and Yunhao You contributed equally to this work. Summary Statement Our study showed that with the presence of orthosilicic 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. * Yunzheng Chen [email protected] 1
Department of Spine Surgery, Qilu Hospital of Shandong University, Jinan, China
2
Department of traumatic Orthopedics, West Branch of Shandong Provincial Hospital, Jinan, China
3
Department of Spine Surgery, Linyi Central Hospital, Linyi, China
fracture. Osteoporosis fracture has the characteristics of high morbidity,
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