Combined effects of fibroblast growth factor 2 and dexamethasone on differentiation of human cementoblasts
1Department of Orthodontics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology; National Clinical Research Center of Stomatology Shanghai 200011, China.
Abstract:
Fibroblast growth factor 2 (FGF-2) is known to play a pivotal role in bone remodeling and osteogenesis. Dexamethasone is a potent modulator of osteogenic differentiation and can increase the bone formation capacity of cementoblasts. However, the combined effects of FGF-2 and dexamethasone on cementoblasts and the way they regulate the activities of cementoblasts have not been fully understood. The aim of this study was to clarify and investigate the effects of the combination of FGF-2 and dexamethasone on growth and differentiation in human cementoblasts and to determine the underlying mechanism. A series of experiments including MTT, alkaline phosphatase (ALP) activity, alizarin red staining, RT-PCR, and Western blot were carried out to evaluate the proliferation and differentiation of cementoblasts. In addition, the changes of Wnt signaling pathway molecules were checked to analyze the possible mechanism. Compared to the treatment of cementoblasts with either FGF 2 or dexamethasone alone, the combination of FGF-2 and dexamethasone synergistically increased cell proliferation, ALP activity, nodule formation, and expression of differentiation markers. In addition, FGF 2 and dexamethasone enhanced expression of Wnt3a, Runx2, β-catenin, and p-GSK-3β, all of which were inhibited by DKK1. Taken together, FGF-2 and dexamethasone act synergistically, enhancing each other's ability to stimulate cementoblast growth and differentiation via Wnt signaling pathways. These results support the therapeutic potential of a combination strategy for facilitating cementogenesis and aiding periodontal regeneration.
