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/b-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 bcatenin expression in newly formed bone area. In this study, 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;29:981-991 Disclosure of potential conflicts of interest is found at the end of this article.

Optogenetics has been widely applied as a cell‐specific technique with high temporal resolution for the modulation of neural circuitry in vivo, offering potential novel treatments for neuropsychiatric diseases. However, to date, the most widely used optogenetics waveguides remain silica optical fibers, which may lead to a mismatch in the mechanical properties between the implants and neural tissues. To resolve this issue, alginate‐polyacrylamide hydrogel optical fibers can be fabricated in a simplified one‐step process, and they show significantly improved characteristics for the in vivo optogenetic applications, including low light‐propagation loss and Young's modulus, and high stretchability. After the expression of AAV‐CaMKIIα‐ChR2‐mCherry, blue light pulses are delivered into hippocampus using a hydrogel‐optrode array, and frequency‐dependent neural responses can be observed. Moreover, optogenetic stimulation through the chronic implanted hydrogel optical fibers in the primary motor cortex can considerably modulate the animal's behavior. Hydrogel fibers significantly alleviate tissue response at the implant/neural interface, compared with that observed using the silica optical fibers. Taken together, the results of this study demonstrate the feasibility and advantages of the hydrogel optical fiber use for chronic optogenetic modulation in free‐moving animals. Hydrogel implant use may allow the development of novel therapeutic strategies for the treatment of neuropsychiatric disorders.