title: Osteogenic effect of interleukin-11 and synergism with ascorbic acid in human periodontal ligament cells.
abstract: OBJECTIVE
  Human periodontal ligament cells are considered to be a key cell type in the regeneration of periodontal tissues because of their unique localization and stem cell-like properties. Interleukin-11 is a multifunctional cytokine known to participate actively in bone metabolism. The purpose of this study was to examine the effect of interleukin-11 on the osteoblastic differentiation of periodontal ligament cells.
  
  
  METHODS
  Cultured periodontal ligament cells were stimulated with interleukin-11 and/or ascorbic acid, with or without inhibitors for type 1 collagen, janus kinase/signal transducers and activator of transcription, and mitogen-activated protein kinase (MAPK). Osteoblastic differentiation was investigated by examining the alkaline phosphatase activity and gene expression of Runx2, osteocalcin and bone sialoprotein using reverse transcription-polymerase chain reaction. Type 1 collagen and tissue inhibitor of metalloproteinase-1 production were measured using enzyme-linked immunosorbent assays.
  
  
  RESULTS
  Interleukin-11 enhanced alkaline phosphatase activity and Runx2, osteocalcin and bone sialoprotein gene expression in the presence of ascorbic acid. Interleukin-11 induced type 1 collagen and tissue inhibitor of metalloproteinase-1 production in periodontal ligament cells. Type 1 collagen inhibitor completely inhibited the alkaline phosphatase activity enhanced by interleukin-11 and ascorbic acid. Furthermore, janus kinase/signal transducers and activator of transcription and MAPK signaling inhibitors reduced interleukin-11/ascorbic acid-induced alkaline phosphatase activity in periodontal ligament cells.
  
  
  CONCLUSIONS
  Interleukin-11/ascorbic acid induced the osteoblastic differentiation of periodontal ligament cells through type 1 collagen production and janus kinase/signal transducers and activator of transcription, and MAPK signaling pathways were involved in this process. These findings suggest that interleukin-11 may function as an osteopromotive cytokine, stimulating the osteoblastic differentiation of periodontal ligament cells mainly through the synthesis of type 1 collagen and possibly by the induction of tissue inhibitor of metalloproteinase-1.
authors.affiliation: Periodontology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors.forename: E R
authors.initials: ER
authors.lastname: Leon
authors.forename: K
authors.initials: K
authors.lastname: Iwasaki
authors.forename: M
authors.initials: M
authors.lastname: Komaki
authors.forename: T
authors.initials: T
authors.lastname: Kojima
authors.forename: I
authors.initials: I
authors.lastname: Ishikawa
mesh_terms: D000469:Alkaline Phosphatase / Q000096:biosynthesis; D001205:Ascorbic Acid / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D004357:Drug Synergism; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D017370:Interleukin-11 / Q000494:pharmacology / Q000502:physiology*; D053612:Janus Kinases / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin / Q000096:biosynthesis; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000096:biosynthesis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis
chemical_list: D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; D017370:Interleukin-11; C493709:RUNX2 protein, human; D012795:Sialoglycoproteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D015675:Osteocalcin; D053612:Janus Kinases; D000469:Alkaline Phosphatase; D001205:Ascorbic Acid