title: Biphasic silica/apatite co-mineralized collagen scaffolds stimulate osteogenesis and inhibit RANKL-mediated osteoclastogenesis.
abstract: The effects of a biphasic mineralized collagen scaffold (BCS) containing intrafibrillar silica and apatite on osteogenesis of mouse mesenchymal stem cells (mMSCs) and inhibition of receptor activator of nuclear factor κB ligand (RANKL)-mediated osteoclastogenesis were investigated in the present study. mMSCs were cultured by exposing to BCS for 7 days for cell proliferation/viability examination, and stimulated to differentiate in osteogenic medium for 7-21 days for evaluation of alkaline phosphatase activity, secretion of osteogenic deposits and expression of osteoblast lineage-specific phenotypic markers. The effect of BCS-conditioned mMSCs on osteoclastogenesis of RAW 264.7 cells was evaluated by tartrate-resistant acid phosphatase staining and resorption pit analysis. The contributions of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K) signal transduction pathways to osteogenesis of mMSCs and their osteoprotegerin (OPG) and RANKL expressions were also evaluated. Compared with unmineralized, intrafibrillarly-silicified or intrafibrillarly-calcified collagen scaffolds, BCS enhanced osteogenic differentiation of mMSCs by activation of the extracellular signal regulated kinases (ERK)/MAPK and p38/MAPK signaling pathways. After mMSCs were exposed to BCS, they up-regulated OPG expression and down-regulated RANKL expression through activation of the p38/MAPK and PI3K/protein kinase B (Akt) pathways, resulting in inhibition of the differentiation of RAW 264.7 cells into multinucleated osteoclasts and reduction in osteoclast function. These observations collectively suggest that BCS has the potential to be used in bone tissue engineering when the demand for anabolic activities is higher than catabolic metabolism during the initial stage of wound rehabilitation.
authors: State Key Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
authors: Kai
authors: K
authors: Jiao
authors: State Key Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
authors: Li-na
authors: LN
authors: Niu
authors: Department of Stomatology, Affiliated Hospital of Academy of Military Medical Science, Beijing, China.
authors: Qi-hong
authors: QH
authors: Li
authors: State Key Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
authors: Fa-ming
authors: FM
authors: Chen
authors: Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors: Wei
authors: W
authors: Zhao
authors: Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors: Jun-jie
authors: JJ
authors: Li
authors: State Key Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, China. Electronic address: jhchen@fmmu.edu.cn.
authors: Ji-hua
authors: JH
authors: Chen
authors: College of Dental Medicine, Georgia Reagents University, Augusta, GA, USA.
authors: Christopher W
authors: CW
authors: Cutler
authors: College of Dental Medicine, Georgia Reagents University, Augusta, GA, USA.
authors: David H
authors: DH
authors: Pashley
authors: College of Dental Medicine, Georgia Reagents University, Augusta, GA, USA. Electronic address: ftay@gru.edu.
authors: Franklin R
authors: FR
authors: Tay
mesh_terms: D000818:Animals; D018786:Bone Substitutes / Q000138:chemical synthesis; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D017886:Durapatite / Q000737:chemistry; D004867:Equipment Design; D019544:Equipment Failure Analysis; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008903:Minerals / Q000737:chemistry; D010006:Osteoblasts / Q000166:cytology* / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology* / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology; D053245:RANK Ligand / Q000378:metabolism; D012822:Silicon Dioxide / Q000737:chemistry*; D054457:Tissue Scaffolds
chemical_list: D018786:Bone Substitutes; D008903:Minerals; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D012822:Silicon Dioxide; D017886:Durapatite
keywords: Hydroxyapatite; Intrafibrillar mineralization; Osteoclastogenesis; Osteogenesis; Osteoprotegerin