title: Biological Silicon Stimulates Collagen Type 1 and Osteocalcin Synthesis in Human Osteoblast-Like Cells Through the BMP-2/Smad/RUNX2 Signaling Pathway.
abstract: Silicon is essential for bone formation. A low-silicon diet leads to bone defects, and numerous animal models have demonstrated that silicon supplementation increases bone mineral density (BMD) and reduces bone fragility. However, the exact mechanism of this action has not been characterized. In this study, we aimed to determine the role of biological silicon in the induction of osteoblast differentiation and the possible underlying mechanism. We examined whether orthosilicic acid promotes collagen type 1 (COL-1) and osteocalcin synthesis through the bone morphogenetic protein-2 (BMP-2)/Smad1/5/runt-related transcription factor 2 (RUNX2) signaling pathway by investigating its effect in vitro at several concentrations on COL-1 and osteocalcin synthesis in human osteosarcoma cell lines (MG-63 and U2-OS). The expression of relevant proteins was detected by Western blotting following exposure to noggin, an inhibitor of BMP-2. In MG-63 cells, immunofluorescence methods were applied to detect changes in the expression of BMP-2, phosphorylated Smad1/5 (P-Smad1/5), and RUNX2. Furthermore, rat bone mesenchymal stem cells (BMSCs) were used to determine the effect of orthosilicic acid on osteogenic differentiation. Exposure to 10 μM orthosilicic acid markedly increased the expression of BMP-2, P-Smad1/5, RUNX2, COL-1, and osteocalcin in osteosarcoma cell lines. Enhanced ALP activity and the formation of mineralized nodules were also observed under these conditions. Furthermore, preconditioning with noggin inhibited the silicon-induced upregulation of P-Smad1/5, RUNX2, and COL-1 expression. In conclusion, the BMP-2/Smad1/5/RUNX2 signaling pathway participates in the silicon-mediated induction of COL-1 and osteocalcin synthesis, and orthosilicic acid promotes the osteogenic differentiation of rat BMSCs.
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, No. 107, Wen Hua Xi Road, Ji'nan, Shandong Province, 250012, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, No. 107, Wen Hua Xi Road, Ji'nan, Shandong Province, 250012, China.
authors.forename: Guangjun
authors.initials: G
authors.lastname: Jiao
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, No. 107, Wen Hua Xi Road, Ji'nan, Shandong Province, 250012, China.
authors.forename: Haichun
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, No. 107, Wen Hua Xi Road, Ji'nan, Shandong Province, 250012, China.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, No. 107, Wen Hua Xi Road, Ji'nan, Shandong Province, 250012, China.
authors.forename: Shangzhi
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, No. 107, Wen Hua Xi Road, Ji'nan, Shandong Province, 250012, China.
authors.forename: Qingshi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, No. 107, Wen Hua Xi Road, Ji'nan, Shandong Province, 250012, China.
authors.forename: Daxia
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, No. 107, Wen Hua Xi Road, Ji'nan, Shandong Province, 250012, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, No. 107, Wen Hua Xi Road, Ji'nan, Shandong Province, 250012, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, No. 107, Wen Hua Xi Road, Ji'nan, Shandong Province, 250012, China. qilucyz@yeah.net.
authors.forename: Yunzhen
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000096:biosynthesis*; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D015675:Osteocalcin / Q000096:biosynthesis*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D012825:Silicon / Q000494:pharmacology*; D051898:Smad1 Protein / Q000378:metabolism*; D051902:Smad5 Protein / Q000378:metabolism*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; C497399:SMAD1 protein, human; C497797:SMAD5 protein, human; D051898:Smad1 Protein; D051902:Smad5 Protein; D015675:Osteocalcin; D012825:Silicon
keywords: Bone morphogenetic protein-2 (BMP-2); Orthosilicic acid; Osteoporosis; Phosphorylated Smad1/5 (P-Smad1/5); Runt-related transcription factor 2 (RUNX2); Smad1/5