Dental Pulp Stem Cell Transplantation with 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside Accelerates Alveolar Bone Regeneration in Rats

Chi-Yu Lin; Po-Jan Kuo; Yu-Tang Chin; I-Tsen Weng; Hao-Wei Lee; Haw-Ming Huang; Hung-Yun Lin; Chao-Nan Hsiung; Ya-Hui Chan; Sheng-Yang Lee

doi:10.1016/j.joen.2018.12.019

Dental Pulp Stem Cell Transplantation with 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside Accelerates Alveolar Bone Regeneration in Rats

J Endod. 2019 Apr;45(4):435-441. doi: 10.1016/j.joen.2018.12.019. Epub 2019 Mar 7.

Authors

Chi-Yu Lin¹, Po-Jan Kuo², Yu-Tang Chin³, I-Tsen Weng⁴, Hao-Wei Lee⁵, Haw-Ming Huang⁶, Hung-Yun Lin³, Chao-Nan Hsiung⁷, Ya-Hui Chan⁶, Sheng-Yang Lee⁸

Affiliations

¹ School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; Center for Tooth Bank and Dental Stem Cell Technology, Taipei Medical University, Taipei, Taiwan.
² Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan.
³ Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan; PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
⁴ School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; Center for Tooth Bank and Dental Stem Cell Technology, Taipei Medical University, Taipei, Taiwan; Department of Dentistry, Wan-Fang Medical Center, Taipei Medical University, Taipei, Taiwan.
⁵ Department of Medicine, Taipei Veterans of General Hospital, Taipei, Taiwan.
⁶ School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
⁷ College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
⁸ School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; Center for Tooth Bank and Dental Stem Cell Technology, Taipei Medical University, Taipei, Taiwan; Department of Dentistry, Wan-Fang Medical Center, Taipei Medical University, Taipei, Taiwan. Electronic address: seanlee@tmu.edu.tw.

PMID: 30851933
DOI: 10.1016/j.joen.2018.12.019

Abstract

Introduction: Although the therapeutic potential of human dental pulp stem cells (hDPSCs) has been studied for bone regeneration, the therapeutic efficiency needs further consideration and examinations for clinical applications. Thus, the aims of this study were to evaluate the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) on the osteogenic differentiation of hDPSCs and to examine the therapeutic efficiency of the THSG-enhanced osseous potential of hDPSCs in alveolar bony defects of rats.

Methods: Expressions of osteogenic messenger RNAs (including ALP, RUNX2, BGLAP, and AMBN) were examined by quantitative real-time polymerase chain reaction. Alizarin red S staining was conducted to analyze THSG-induced mineralization of hDPSCs. To investigate the regenerative effects of THSG-treated hDPSCs on dental alveolar bone, bony defects were created in male Sprague-Dawley rats. Defects were treated with Matrigel (Corning Inc, Corning, NY), hDPSCs, or hDPSCs + THSG. After 2 weeks, defect healing was evaluated by micro-computed tomographic and histologic analyses.

Results: In the cell model, THSG induced osteogenesis-associated genes (ALP, RUNX2, and BGLAP) and an enamel-related gene (AMBN), resulting in mineralization as detected by alizarin red S staining after 2 weeks of treatment. In the animal model, THSG increased all parameters of bone formation (the relative bone volume, trabecular thickness, trabecular number, and trabecular separation) in alveolar bony defects of rats. THSG not only improved the quality of newly formed bone but also the quantity of new bone.

Conclusions: These results showed important findings in revealing the THSG-enhanced osteogenic differentiation of hDPSCs and THSG-facilitated bone regeneration, which may provide an alternative option for cell-based regenerative therapy.

Keywords: 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside; Alkaline phosphatase; bone regeneration; human dental pulp stem cells.

MeSH terms

Adolescent
Adult
Alveolar Bone Loss / therapy*
Alveolar Process / physiology*
Animals
Bone Regeneration / drug effects*
Bone Regeneration / physiology*
Cell Differentiation*
Dental Pulp / cytology*
Disease Models, Animal
Female
Glucosides / pharmacology*
Humans
Male
Osteogenesis* / drug effects
Osteogenesis* / genetics
Rats, Sprague-Dawley
Regenerative Medicine / methods
Stem Cell Transplantation*
Stem Cells / physiology*
Stilbenes / pharmacology*
Stimulation, Chemical
Young Adult

Substances

Glucosides
Stilbenes
2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside