Naringenin stimulates osteogenic/odontogenic differentiation and migration of human dental pulp stem cells
Yeon Kim, Hyun-Joo Park, Mi-Kyoung Kim, Yong‐Il Kim, Hyung Joon Kim, Soo‐Kyung Bae, Jacques E. Nör, Moon‐Kyoung Bae
Abstract
Naringenin, a naturally occurring flavanone in citrus fruits, regulates bone formation by bone marrow-derived mesenchymal stem cells. The purpose of this study was to characterize the effects of naringenin on some biological behaviors of human dental pulp stem cells (HDPSCs). HDPSCs were cultured in osteogenic differentiation medium and osteo/odontogenic differentiation and mineralization were analyzed by alkaline phosphatase (ALP) staining and Alizarin Red S (ARS) staining. The migration of HDPSCs was evaluated by transwell chemotactic migration assays and scratch wound healing migration assay. Using tooth slice/scaffold model, we assessed the in vivo odontogenic differentiation potential of HDPSCs. We have demonstrated that naringenin increases the osteogenic/odontogenic differentiation of HDPSCs through regulation of osteogenic-related proteins and the migratory ability of HDPSCs through stromal cell derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) axis. Moreover, naringenin promotes the expression of dentin matrix acidic phosphoprotein-1 (DMP-1) and dentin sialophosphoprotein (DSPP) in HDPSCs seeded on tooth slice/scaffolds that are subcutaneously implanted into immunodeficient mice. Our present study suggests that naringenin promotes migration and osteogenic/odontogenic differentiation of HDPSCs and may serve as a promising candidate in dental tissue engineering and bone regeneration.