Objective:
The regeneration capacity of the osteoporotic bones is generally lower than that of the normal bones for craniofacial bones. Current methods of bone defect treatment for osteoporosis are not always satisfactory. Strontium ranelate (Sr) is an approved drug that can reduce the risk of bone fracture, which is attributed to its dual function in increasing the bone formation and decreasing the bone resorption. However, the molecular mechanisms of strontium underlying such beneficial effects were still not fully understood.

Materials and Methods:
Based on the hypothesis that the combination of stem cells and Sr may have synergetic effects on osteoporotic bone regeneration, the porous Sr substituted hydroxyapatite (SrHAP) cryogel scaffolds were developed with the goals to promote osteoporotic bone regeneration in craniofacial bone defects in rats. The effects of the SrHAP on osteogenic differentiation of adipose stem cells derived from ovariectomized rats (ASCsOVX) were investigated. The osteogenic potential was also evaluated using an alveolar defect model in rats.

Results:
We found that strontium could enhance the osteogenic differentiation of the ASCsOVX, with upregulated extracellular matrix (ECM) gene expression and activated Wnt/b-catenin pathway. The in vivo experiments revealed that ASCsOVX/SrHAP stimulated bone regeneration in a critical sized alveolar bone defect of OVX rat model.

Conclusions:
The osteoporotic bone regeneration in critically craniofacial bone defects of OVX rat model showed that Sr not only have superior osteoinductive activity to enhance early bone formation but could also promote in vivo bone formation through regulating of Wnt/Catenin signaling. Our studies demonstrated that the Sr scaffold combine with ASCsOVX might be a new strategy for the regeneration of craniofacial bone in osteoporosis.

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