The New Therapeutic Strategy of 2, 3, 5, 4’-Tetrahydroxystilbene-2-O-Β-D-Glucoside (Thsg) Derivatives on Human Dental Pulp Stem Cells-Based Periodontal Treatment(3/3)

In the past few years, there were several populations of MSCs identified in numerous dental tissues, including dental pulp stem cells (DPSC). The therapeutic potential of DPSCs has been reported, but the therapeutic efficiency needs further consideration and examinations. Periodontal disease is a common bacteria-induced inflammatory disease and damages the surrounding hard and soft tissue structures. Various herb-extracted compounds have been applied currently to attenuate periodontal destruction of periodontal disease. To rebuild the lost periodontal attachment is the critical goal of periodontal therapy and the dental stem cells have been reported as candidates for restore the lost periodontal tissue. Resveratrol as well as 2, 3, 5, 4’-Tetrahydroxystilbene-2-O-β-D-glucoside (THSG) is one kind of polyphenolic phytoestrogen. They are structure similar polyhydroxy stilbene compounds. Both are known to exert numerous pharmacological activities, including anti-oxidation, anti-inflammation, anti-cancer, cardioprotection, vasoprotection, promoting osteogenesis and stimulating stem cell proliferation. In addition, our preliminary results indicated that resveratrol and THSG stimulated gingival fibroblast proliferation. However, there is no study of their effects on dental pulp stem cells. In this present 3-year proposal, the main aims are 1) to evaluate the effect of resveratrol and its derivative, THSG, on the induced cell proliferation and osseous differentiation in DPSCs, 2) to examine the mechanisms of resveratrol- or THSG-enhanced proliferative and differentiated potentials on DPSCs, and 3) to in vivo test the therapeutic potential of DPSCs combined with resveratrol- or THSG in the periodontal defect of rats. To address aims of this proposal, in the aim 1 (first year): hDPSCs will be isolated and cultured, and then treated them with resveratrol or THSG. Cell proliferation effect will be evaluated by MTT assay and QPCR; the osseous differentiation will be examined by alkaline phosphatase enzyme activity assay, immunocytochemistry and QPCR. In the aim 2 (second year), AMPK or Sirt1 inhibitors will be treated cells to evaluate the mechanism of these two stilbene compounds in cell proliferation or osseous differentiation, the MTT assay, immunocytochemistry, chemical staining of calcium, and QPCR will be applied. In the aim 3 (final year), surgical supra-infrabony periodontal defects of rats will be created to evaluate the regenerative effects of resveratrol or THSH in hDPSCs-based therapy. The Microcomputed tomography imaging and histological examination will be used.