4 w3 [) I$ _, rStrontium Enhances Osteogenic Differentiation of Mesenchymal Stem Cells and In Vivo Bone Formation by Activating Wnt/Catenin Signaling$ N% w. g! ^6 O) G
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FAN YANG, DAZHI YANG, JIE TU, QIXIN ZHENG, LINTAO CAI, LIPING WANGa a D% x+ U M' a6 ^+ b y
1 V$ V7 N" p! k5 t) y7 N$ |Research Center for Neural Engineering, Shenzhen Key Laboratory for Neuropsychiatric Modulation,Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; b2 o/ d1 }8 v* b0 a' t3 eDepartment of Orthopaedics, Union Hospital, Tongji Medical College, HuaZhong University of Science and Technology, Wuhan, China; 2 q' W' S. d4 C& j6 w8 j" XShenzhen Key Laboratory for Cancer Nanotechnology, Shenzhen Institutes of Advanced Technology, $ M7 h2 }( f1 T- W2 OChinese Academy of Sciences, Shenzhen, China 1 F: u' }" F& M+ [) \* _$ C. W : ~, {7 t5 ^2 |. o. K4 s 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 . i7 a; t: q, h- mosteoblast activity and inhibit the osteoclast activity.However, the molecular mechanisms of strontium underly- ing such beneficial effects were still not fully understood.# ]- ?. n& P( m; ]
4 a- G8 b% h; R& F+ ~/ A 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- [8 J" G: J7 E, }* u* b
the osteogenic differentiation of the MSCs, with upregulated extracellular matrix (ECM) gene expression and activated Wnt/b-catenin pathway. After transplanting the collagen-strontium-substituted hydroxyapatite scaffold into the bone defect region, histology and computed to mography 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 bcatenin expression in newly formed bone area. In this ! l+ q- \/ N( dstudy, we showed for the first time that strontium could stimulate the b-catenin expression in vitro and in vivo, which might contribute to the enhanced osteogenic differentiation of MSCs and in vivo bone formation. STEM CELLS 2011;29:981–9917 z2 F) s6 O/ V6 A
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