title: Increased osteogenic differentiation of periodontal ligament stem cells on polydopamine film occurs via activation of integrin and PI3K signaling pathways.
abstract: OBJECTIVE
  Mussel-inspired polydopamine (PDA) is known to be an effective bioadhesive and bioactive material for controlling stem cell fate, which is important in stem cell-based regenerative medicine; however, the effect of PDA on osteogenic differentiation of periodontal ligament stem cells (PDLSCs) is not fully understood. In this study, we investigated the osteoinductive effect of PDA on PDLSCs and examined how this phenomenon is encouraged.
  
  
  METHODS
  Osteogenic induction of PDLSCs was established by culturing cells on PDA film or on an uncoated polystyrene surface as a control. Osteogenic differentiation of PDLSCs was assessed by measurement of intracellular calcium levels and alkaline phosphatase (ALP) activity as well as by evaluation of protein expression of osteocalcin (OCN), osterix (OSX), and runt-related transcription factor 2 (RUNX2).
  
  
  RESULTS
  The PDLSCs cultured on PDA film showed higher osteogenic activity than those on the control surface. Moreover, PDLSCs on PDA film expressed increased levels of the integrin adhesion receptors integrin α5 and β1 compared to control cells. Expression of one isoform of the intracellular signaling protein phosphatidylinositol-3-kinase (PI3K), p110γ, was increased in PDLSCs on PDA film in a PDA dose-dependent manner. This signaling protein was found to interact with integrin β1, demonstrating integrin-linked PI3K activation in response to PDA. Finally, the blockage of PI3K reduced the PDA-induced osteogenic activity of PDLSCs.
  
  
  CONCLUSIONS
  our findings suggest that the bioadhesive PDA stimulates osteogenic differentiation of PDLSCs via activation of the integrin α5/β1 and PI3K signaling pathways.
authors.affiliation: Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Dongdaemun-gu, Seoul, South Korea.
authors.forename: Jeong Seok
authors.initials: JS
authors.lastname: Lee
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Yi
authors.forename: Seong Yeong
authors.initials: SY
authors.lastname: An
authors.forename: Jung Sun
authors.initials: JS
authors.lastname: Heo
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D016023:Integrins / Q000378:metabolism*; D015675:Osteocalcin / Q000378:metabolism / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D010513:Periodontal Ligament / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011108:Polymers / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
chemical_list: D007211:Indoles; D016023:Integrins; D011108:Polymers; C568283:polydopamine; D015675:Osteocalcin; D019869:Phosphatidylinositol 3-Kinases; D000469:Alkaline Phosphatase