title: Adiponectin regulates functions of gingival fibroblasts and periodontal ligament cells.
abstract: OBJECTIVE
  Adiponectin is a cytokine constitutively produced by adipocytes and exhibits multiple biological functions by targeting various cell types. However, the effects of adiponectin on primary gingival fibroblasts and periodontal ligament cells are still unexplored. Therefore, we investigated the effects of adiponectin on gingival fibroblasts and periodontal ligament cells.
  
  
  METHODS
  The expression of adiponectin receptors (AdipoR1 and AdipoR2) on human gingival fibroblasts (HGFs), mouse gingival fibroblasts (MGFs) and human periodontal ligament (HPDL) cells was examined using RT-PCR and western blotting. HGFs and MGFs were stimulated with interleukin (IL)-1β in the presence or absence of adiponectin, and the expression of IL-6 and IL-8 at both mRNA and protein levels was measured by real-time PCR and ELISA, respectively. Furthermore, small interfering RNAs (siRNAs) in MGFs were used to knock down the expression of mouse AdipoR1 and AdipoR2. The effects of adiponectin on the expression of alkaline phosphatase (ALP) and runt-related transcription factor 2 (Runx2) genes were evaluated by real-time PCR. Mineralized nodule formation of adiponectin-treated HPDL cells was revealed by Alizarin Red staining.
  
  
  RESULTS
  AdipoR1 and AdipoR2 were expressed constitutively in HGFs, MGFs and HPDL cells. Adiponectin decreased the expression of IL-6 and IL-8 in IL-1β-stimulated HGFs and MGFs. AdipoR1 siRNA in MGFs revealed that the effect of adiponectin on reduction of IL-6 expression was potentially mediated via AdipoR1. Adiponectin-treated HPDL cells promoted the expression of ALP and Runx2 mRNAs and up-regulated ALP activity. Furthermore, adiponectin enhanced mineralized nodule formation of HPDL cells.
  
  
  CONCLUSIONS
  Our observations demonstrate that adiponectin exerts anti-inflammatory effects on HGFs and MGFs, and promotes the activities of osteoblastogenesis of HPDL cells. We conclude that adiponectin has potent beneficial functions to maintain the homeostasis of periodontal health, improve periodontal lesions, and contribute to wound healing and tissue regeneration.
authors.affiliation: Division of Oral Biology and Disease Control, Department of Periodontology, Osaka University Graduate School of Dentistry, Yamadaoka, Suita, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iwayama
authors.forename: M
authors.initials: M
authors.lastname: Yanagita
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: K
authors.initials: K
authors.lastname: Sawada
authors.forename: M
authors.initials: M
authors.lastname: Ozasa
authors.forename: M
authors.initials: M
authors.lastname: Kubota
authors.forename: K
authors.initials: K
authors.lastname: Miki
authors.forename: Y
authors.initials: Y
authors.lastname: Kojima
authors.forename: M
authors.initials: M
authors.lastname: Takedachi
authors.forename: M
authors.initials: M
authors.lastname: Kitamura
authors.forename: Y
authors.initials: Y
authors.lastname: Shimabukuro
authors.forename: T
authors.initials: T
authors.lastname: Hashikawa
authors.forename: S
authors.initials: S
authors.lastname: Murakami
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D000880:Anthraquinones; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002113:Calcification, Physiologic / Q000187:drug effects; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004396:Coloring Agents; D050659:Core Binding Factor Alpha 1 Subunit / Q000032:analysis; D005347:Fibroblasts / Q000187:drug effects*; D020868:Gene Silencing; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010006:Osteoblasts / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects*; D034741:RNA, Small Interfering / Q000494:pharmacology; D054419:Receptors, Adiponectin / Q000032:analysis / Q000235:genetics
chemical_list: C499918:ADIPOQ protein, human; C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; C499919:Adipoq protein, mouse; D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; D004396:Coloring Agents; D050659:Core Binding Factor Alpha 1 Subunit; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D034741:RNA, Small Interfering; C493709:RUNX2 protein, human; D054419:Receptors, Adiponectin; C493716:Runx2 protein, mouse; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse; C004468:Alizarin Red S; D000469:Alkaline Phosphatase