title: Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells.
abstract: Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration.
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Sawada
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka, Japan. Electronic address: takedati@dent.osaka-u.ac.jp.
authors.forename: Masahide
authors.initials: M
authors.lastname: Takedachi
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Morimoto
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Ozasa
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Iwayama
authors.affiliation: Medical Center for Translational Research, Osaka University Hospital, Osaka, Japan.
authors.forename: Chun Man
authors.initials: CM
authors.lastname: Lee
authors.affiliation: Research on Disease Bioresources, Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, Osaka, Japan.
authors.forename: Hanayuki
authors.initials: H
authors.lastname: Okura
authors.affiliation: Research on Disease Bioresources, Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, Osaka, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Matsuyama
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kitamura
authors.affiliation: Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Murakami
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D003739:Dental Cementum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; C066855:HGF protein, human; D018976:Insulin-Like Growth Factor Binding Protein 6; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; D000469:Alkaline Phosphatase
keywords: Adipose tissue; Periodontal ligament; Progenitor cell; Regeneration