title: Insulin-like growth factor 1 (IGF1) affects proliferation and differentiation and wound healing processes in an inflammatory environment with p38 controlling early osteoblast differentiation in periodontal ligament cells.
abstract: OBJECTIVE
  The objective of this study was to investigate effects of insulin-like growth factor 1 (IGF1) on proliferation, wound healing and differentiation processes of human periodontal ligament (PDL) cells under inflammatory conditions and whether the protective, anabolic effects of IGF1 can attenuate unfavorable effects of interleukin-1β (IL-1β).
  
  
  METHODS
  Inflammation was mimicked through cell stimulation with IL-1β. PDL cells were characterized in respect to the presence of components of the IGF system and the responsive potential on IL-1β incubation. Gene expression levels were analyzed by quantitative real-time PCR. Cellular localization of target proteins was visualized using fluorescent-based immunohistochemistry. Effects on cell division were investigated by proliferation assays. Wound healing was analyzed using light microscopic techniques. Differentiation was quantified by measuring biomineralization and osteoblast-specific alkaline phosphatase enzyme activity.
  
  
  RESULTS
  PDL cell proliferation and wound healing were positively affected by IGF1 and the combination of IGF1 with IL-1β, while only IL-1β showed negative effects. Biomineralization was enhanced by IGF1, IL-1β, and the combination of both stimulants. Osteoblast differentiation was increased by IL-1β and the combination of IL-1β with IGF1, whereas only IGF1 negatively affected ALP activity. Phosphorylation of p38 was regulated by IL-1β and IGF1.
  
  
  CONCLUSIONS
  The data presented in this work showed a potential of IGF1 to improve wound healing and proliferation processes and to sustain cell differentiation under inflammatory stimuli in PDL cells.
authors: Department of Prosthodontics, Preclinical Education and Material Science, University of Bonn, Welschnonnenstr. 17, 53111 Bonn, Germany; Department of Orthodontics, University of Bonn, Bonn, Germany; Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany; Department of Oral & Maxillofacial Plastic Surgery, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
authors: Jan
authors: J
authors: Reckenbeil
authors: Department of Prosthodontics, Preclinical Education and Material Science, University of Bonn, Welschnonnenstr. 17, 53111 Bonn, Germany.
authors: Dominik
authors: D
authors: Kraus
authors: Department of Prosthodontics, Preclinical Education and Material Science, University of Bonn, Welschnonnenstr. 17, 53111 Bonn, Germany.
authors: Helmut
authors: H
authors: Stark
authors: Department of Orthodontics, University of Bonn, Bonn, Germany.
authors: Birgit
authors: B
authors: Rath-Deschner
authors: Department of Orthodontics, University of Bonn, Bonn, Germany.
authors: Andreas
authors: A
authors: Jäger
authors: Department of Oral & Maxillofacial Plastic Surgery, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
authors: Matthias
authors: M
authors: Wenghoefer
authors: Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany. Electronic address: jochen.winter@ukb.uni-bonn.de.
authors: Jochen
authors: J
authors: Winter
authors: Department of Orthodontics, University of Bonn, Bonn, Germany.
authors: Werner
authors: W
authors: Götz
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D002113:Calcification, Physiologic / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction; D014070:Tooth / Q000166:cytology / Q000187:drug effects; D020032:Tyrphostins / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D020032:Tyrphostins; C447031:tyrphostin AG 1024; D007334:Insulin-Like Growth Factor I; D048051:p38 Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase
keywords: Biomineralization; IGF-1; IL-1β; Inflammation; p38