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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\/\u03b2-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 \u03b2-catenin expression in newly formed bone area. In this study, we showed for the first time that strontium could stimulate the \u03b2-catenin expression in vitro and in vivo, which might contribute to the enhanced osteogenic differentiation of MSCs and in vivo bone formation.<\/jats:p>","DOI":"10.1002\/stem.646","type":"journal-article","created":{"date-parts":[[2011,4,20]],"date-time":"2011-04-20T11:31:36Z","timestamp":1303299096000},"page":"981-991","source":"Crossref","is-referenced-by-count":445,"title":["Strontium Enhances Osteogenic Differentiation of Mesenchymal Stem Cells and In Vivo Bone Formation by Activating Wnt\/Catenin Signaling"],"prefix":"10.1093","volume":"29","author":[{"given":"Fan","family":"Yang","sequence":"first","affiliation":[{"name":"Research Center for Neural Engineering, Shenzhen Key Laboratory for Neuropsychiatric Modulation, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dazhi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Union Hospital, Tongji Medical College, HuaZhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Tu","sequence":"additional","affiliation":[{"name":"Research Center for Neural Engineering, Shenzhen Key Laboratory for Neuropsychiatric Modulation, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qixin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Union Hospital, Tongji Medical College, HuaZhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lintao","family":"Cai","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory for Cancer Nanotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center for Neural Engineering, Shenzhen Key Laboratory for Neuropsychiatric Modulation, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,5,23]]},"reference":[{"key":"2022011210465162100_bib1","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1056\/NEJMoa022436","article-title":"The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis","volume":"350","author":"Meunier","year":"2004","journal-title":"N Engl J Med"},{"key":"2022011210465162100_bib2","doi-asserted-by":"crossref","first-page":"4348","DOI":"10.1016\/j.biomaterials.2006.03.048","article-title":"Strontium-containing hydroxyapatite bioactive bone cement in revision hip arthroplasty","volume":"27","author":"Ni","year":"2006","journal-title":"Biomaterials"},{"issue":"2 suppl 1","key":"2022011210465162100_bib3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.bone.2005.09.023","article-title":"Strontium ranelate: A physiological approach for an improved bone quality","volume":"38","author":"Ammann","year":"2006","journal-title":"Bone"},{"issue":"2 suppl 1","key":"2022011210465162100_bib4","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.bone.2005.07.029","article-title":"Strontium ranelate: A physiological approach for optimizing bone formation and resorption","volume":"38","author":"Marie","year":"2006","journal-title":"Bone"},{"issue":"suppl 3","key":"2022011210465162100_bib5","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.1007\/s00198-002-1343-6","article-title":"Is the calcium receptor a molecular target for the actions of strontium on bone?","volume":"14","author":"Brown","year":"2003","journal-title":"Osteoporos Int"},{"key":"2022011210465162100_bib6","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1074\/jbc.M801668200","article-title":"The calcium-sensing receptor is involved in strontium ranelate-induced osteoclast apoptosis. 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