Abstract
Secreted frizzled-related protein (sFRP)-3 is a negative regulator of Wnt signaling in human mesenchymal stem cells (hMSCs). The present study investigated the effects sFRP-3 on osteogenic differentiation by assessing osteogenic gene expression in hMSCs in vitro and by examining bone regeneration in a rat bone defect model. sFRP-3 treatment induced osteogenic differentiation in hMSCs as determined by alkaline phosphatase, collagen type I, osteocalcin, and Runt-related transcription factor 2 gene expression. hMSCs with or without sFRP-3 were implanted into a rat calvarial bone defect; a radiographic analysis by micro-computed tomography and histological analysis 4 and 8 weeks after implantation showed greater bone regeneration in the sFRP(+) than in the sFRP(−) group. These results suggest that modulation of Wnt signaling contributes to osteogenic differentiation in hMSCs. Specifically, sFRP-3 induces osteoblastic differentiation of cultured MSCs and bone regeneration in a calvarial bone defect, suggesting that it can be a useful agent for the treatment of bone defects.
Highlights
Until recently, autogenous bone grafts were considered the gold standard for the treatment of bone defects resulting from surgery, trauma, and inflammatory disease
Levels of each of these genes associated with osteogenic differentiation were upregulated in human mesenchymal stem cells (hMSCs) treated with Secreted frizzled-related protein (sFRP)-3 as compared to untreated cells (Figure 1)
Transfection of a short interfering RNA against sFRP-3 suppressed ALP activity [21]. These findings along with the present results indicate that Wnt signaling negatively regulates while sFRP-3 activates osteogenic differentiation in hMSCs
Summary
Autogenous bone grafts were considered the gold standard for the treatment of bone defects resulting from surgery, trauma, and inflammatory disease This well-studied procedure has good prognosis but requires an extra surgery at the donor site, which is an additional burden on the patient. Wnt 3a, a canonical Wnt member, induces β-catenin nuclear localization and MSC proliferation while inhibiting osteogenic differentiation. The modulation of Wnt signaling by sFRP-3 has therapeutic implications for the treatment of bone defects, since it may accelerate regeneration and shorten the treatment period and reduce the cost of cell culture. The present study investigated the role of sFRP-3 in the osteogenic potential of hMSCs in vitro and on bone regeneration in vivo in a rat calvarial bone defect model
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