Elevated osteogenic potential of stem cells from inflammatory dental pulp tissues by Wnt4 overexpression for treating bone defect in rats.

Abstract

The osteogenic capacity of inflammatory dental pulp stem cells (DPSCs-IPs) is reported lower than that of normal dental pulp stem cells (DPSCs-NPs). Down-regulation of Wnt4 may be the key factor affecting the osteogenic ability of DPSCs-IPs. In order to prove that the restoration of Wnt4 expression could improve the osteogenic potential of DPSCs-IPs, Wnt4 overexpressed inflammatory dental pulp stem cells (Wnt4-DPSCs-IPs) were performed to reconstruct bone defects in rats. Human DPSCs-IPs were cultured and transfected with Wnt4 overexpression lentiviral vector. Stem cell characterization was performed by flow cytometry and induction of multidirectional differentiation. Wnt4-DPSCs-IPs were loaded onto poly (hydroxybutyrate-co-valerate) (PHBV). The compounds were engrafted into artificially-created defect in alveolar bone. The effectiveness of Wnt4-DPSCs-IPs/PHBV in bone regeneration was assessed by micro-CT and immunohistochemical staining of osteocalcin, a representative osteogenic marker. Collecting data showed that Wnt4 overexpression didn't change stem cell characteristics of DPSCs-IPs. Wnt4-DPSCs-IPs retain osteogenic, adipogenic and chondrogenic differentiation abilities. Wnt4-DPSCs-IPs/PHBV were more effective than DPSCs-IPs/PHBV in repair of rat bone defects by 3 months' post-surgical reconstruction. Restoration of Wnt4 expression could improve the osteogenic potential of DPSCs-IPs. Wnt4 restored DPSCs-IPs may be a feasible resource of seed cells for bone regeneration in future clinical application.