title: Effects of VEGF and FGF-2 on proliferation and differentiation of human periodontal ligament stem cells.
abstract: Human periodontal ligament stem cells (PDLSCs) from extracted third molar teeth are a type of adult stem cell originating from dental tissue. PDLSCs are known to have a self-renewal capacity and multi-lineage differentiation potential. Vascular endothelial growth factor (VEGF), an angiogenic/vasculogenic factor, has been shown to stimulate endothelial cell mitogenesis and cell migration. Another growth factor, fibroblast growth factor-2 (FGF-2), a mitogenic factor, enhances osteogenesis in mesenchymal stem cells (MSCs). This study examines the effects of VEGF and FGF-2 on PDLSCs in vitro and in vivo compared with those on bone marrow stem cells (BMSCs) as a positive control. Treatment of PDLSCs with VEGF increases the accumulation of calcium nodules, alkaline phosphatase (ALP) activity and the formation of hard tissue and up-regulates the mRNA level of runt-related transcription factor 2 (Runx2). In contrast, FGF-2 enhances the proliferation of PDLSCs in vitro in cell culture, where it significantly decreases calcium accumulation and ALP activity and down-regulates the expression of osteogenic gene markers (i.e., Runx2, ALP, type I collagen) involved in osteogenic induction. We have also transplanted PDLSCs with hydroxyapatite/tricalcium phosphate particles (HA/TCP) as carriers for each factor (VEGF, FGF-2) into nude mice and, after 8 weeks, observed the in vivo formation of hard tissue at the dorsal surface. Based on our results, we suggest that VEGF has positive effects on odonto-/osteogenic differentiation in vitro and on the formation of mineralized structure in vivo. FGF-2 might be a powerful promoter of the proliferation of progenitor cells in hard tissue regeneration but exogenous FGF-2 might inhibit terminal differentiation.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, BK21, Craniomaxillofacial Life Science, Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Joo-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Soyoun
authors.initials: S
authors.lastname: Um
authors.forename: Jun-Hyeog
authors.initials: JH
authors.lastname: Jang
authors.forename: Byoung Moo
authors.initials: BM
authors.lastname: Seo
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002130:Calcium Phosphates / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D017886:Durapatite / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010513:Periodontal Ligament / Q000166:cytology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D002130:Calcium Phosphates; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D017886:Durapatite; D000469:Alkaline Phosphatase; C018392:tricalcium phosphate