title: Strontium enhances osteogenic differentiation of mesenchymal stem cells and in vivo bone formation by activating Wnt/catenin signaling.
abstract: Strontium ranelate is a newly approved drug that can reduce the risk of vertebral fracture, which is attributed to its dual function in increasing the bone formation and decreasing the bone resorption. Strontium-containing hydroxyapatite was also demonstrated to stimulate the osteoblast activity and inhibit the osteoclast activity. However, the molecular mechanisms of strontium underlying such beneficial effects were still not fully understood. In this study, we investigated the effects of strontium on the osteogenic differentiation of human mesenchymal stem cells (MSCs) and its related mechanism; its osteogenic potential was also evaluated using a calvarial defect model in rats. We found that strontium could enhance the osteogenic differentiation of the MSCs, with upregulated extracellular matrix (ECM) gene expression and activated Wnt/β-catenin pathway. After transplanting the collagen-strontium-substituted hydroxyapatite scaffold into the bone defect region, histology and computed tomography scanning revealed that in vivo bone formation was significantly enhanced; the quantity of mature and remodeled bone substantially increased and ECM accumulated. Interestingly, strontium induced an increase of β-catenin expression in newly formed bone area. In this study, we showed for the first time that strontium could stimulate the β-catenin expression in vitro and in vivo, which might contribute to the enhanced osteogenic differentiation of MSCs and in vivo bone formation.
authors.affiliation: Research Center for Neural Engineering, Shenzhen Key Laboratory for Neuropsychiatric Modulation, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Dazhi
authors.initials: D
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Tu
authors.forename: Qixin
authors.initials: Q
authors.lastname: Zheng
authors.forename: Lintao
authors.initials: L
authors.lastname: Cai
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D001861:Bone Regeneration; D002454:Cell Differentiation / Q000187:drug effects*; D048430:Cell Shape; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D053495:Osteopontin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D012886:Skull / Q000187:drug effects* / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D013324:Strontium / Q000494:pharmacology*; D054457:Tissue Scaffolds; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D016326:Extracellular Matrix Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D053495:Osteopontin; C025700:strontium chloride; D013324:Strontium