title: Semaphorin 3A induces mesenchymal-stem-like properties in human periodontal ligament cells.
abstract: Periodontal ligament stem cells (PDLSCs) have recently been proposed as a novel option in periodontal regenerative therapy. However, one of the issues is the difficulty of stably generating PDLSCs because of the variation of stem cell potential between donors. Here, we show that Semaphorin 3A (Sema3A) can induce mesenchymal-stem-like properties in human periodontal ligament (PDL) cells. Sema3A expression was specifically observed in the dental follicle during tooth development and in parts of mature PDL tissue in rodent tooth and periodontal tissue. Sema3A expression levels were found to be higher in multipotential human PDL cell clones compared with low-differentiation potential clones. Sema3A-overexpressing PDL cells exhibited an enhanced capacity to differentiate into both functional osteoblasts and adipocytes. Moreover, PDL cells treated with Sema3A only at the initiation of culture stimulated osteogenesis, while Sema3A treatment throughout the culture had no effect on osteogenic differentiation. Finally, Sema3A-overexpressing PDL cells upregulated the expression of embryonic stem cell markers (NANOG, OCT4, and E-cadherin) and mesenchymal stem cell markers (CD73, CD90, CD105, CD146, and CD166), and Sema3A promoted cell division activity of PDL cells. These results suggest that Sema3A may possess the function to convert PDL cells into mesenchymal-stem-like cells.
authors.affiliation: 1 Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, Fukuoka, Japan .
authors.forename: Naohisa
authors.initials: N
authors.lastname: Wada
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Maeda
authors.forename: Daigaku
authors.initials: D
authors.lastname: Hasegawa
authors.forename: Stan
authors.initials: S
authors.lastname: Gronthos
authors.forename: Peter Mark
authors.initials: PM
authors.lastname: Bartold
authors.forename: Danijela
authors.initials: D
authors.lastname: Menicanin
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Fujii
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yoshida
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tomokiyo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Monnouchi
authors.forename: Akifumi
authors.initials: A
authors.lastname: Akamine
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002461:Cell Line, Transformed; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008807:Mice, Inbred BALB C; D010012:Osteogenesis / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology* / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D040121:Semaphorin-3A / Q000494:pharmacology*; D014083:Tooth Germ / Q000187:drug effects / Q000196:embryology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D040121:Semaphorin-3A