Chlorogenic Acid Promotes Osteogenic Differentiation of Human Dental Pulp Stem Cells Through Wnt Signaling.

Periodontal disease (PD) is one of the main causes of periodontal bone resorption and tooth loss in adults. How to repair the alveolar bone effectively has always been a challenge. This study was designed to clarify the effects and the underlying molecular mechanisms of chlorogenic acid (CGA) on osteogenic differentiation of human dental pulp stem cells (hDPSCs). In this study, we used CGA to treat hDPSCs. The osteogenic experiment showed that CGA can promote hDPSCs osteogenic differentiation. RNA-Seq and quantitative real-time polymerase chain reaction showed that CGA treatment enhanced the expression of the osteogenesis genes for frizzled-related protein (FRZB) and pyruvate dehydrogenase kinase 4 (PDK4) and inhibit the expression of the osteoclastogenesis genes such as those for asporin (ASPN) and cytokine-like 1 (CYTL1). Western blot analysis showed that besides FRZB, CGA treatment also caused reduction of both active and total β-catenin, while increased the total calcium/calmodulin-dependent kinase II (CamKII), the phosphorylated CamKII (pCamKII) and the phosphorylated cAMP-response element-binding protein (pCREB). Likely, the increased osteogenesis was associated with reduced canonical Wnt/β-catenin signaling but increased noncanonical Wnt/Ca2+ signaling. The results suggested that CGA can promote the osteogenic differentiation of hDPSCs by regulating Wnt signaling. These findings will serve as a foundation for further studies on how to repair defective alveolar bone for the patients with PD.