title: Lysophosphatidic acid modulates the healing responses of human periodontal ligament fibroblasts and enhances the actions of platelet-derived growth factor.
abstract: BACKGROUND
  Platelet-derived growth factor (PDGF) has been used to promote healing in many in vitro and in vivo models of periodontal regeneration. PDGF interacts extensively with lysophosphatidic acid (LPA). We recently showed that LPA modulates the responses of human gingival fibroblasts to PDGF. The objectives of this study were as follows: 1) to evaluate the basic interactions of LPA with primary human periodontal ligament fibroblasts (PDLFs) alone and with PDGF-BB for promoting PDLF growth and migration; 2) to determine the effects in an in vitro oral wound-healing model; and 3) to identify the LPA receptors (LPARs) expressed by PDLF.
  
  
  METHODS
  PDLF regenerative responses were measured using 1 and 10 microM LPA in the absence or presence of 1 or 10 ng/ml PDGF. Cell proliferation was determined by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and by cell counting. Migration responses were measured using a microchemotaxis chamber. PDLFs were grown to confluence on glass slides, a 3-mm-wide wound was mechanically inflicted, and wound fill on days 4, 6, and 9 was reported. PDLF LPAR expression was determined using Western blotting.
  
  
  RESULTS
  PDLFs exhibited proliferative and chemotactic responses to LPA; these responses were enhanced when LPA and PDGF were present together. LPA plus PDGF elicited complete wound fill. PDLFs express the LPARs LPA(1), LPA(2), and LPA(3).
  
  
  CONCLUSIONS
  To our knowledge, this study provides the first evidence that LPA stimulates human PDLF wound healing responses and interacts positively with PDGF to regulate these actions. These results suggest that LPA and its receptors play important modulatory roles in PDLF regenerative biology.
authors.affiliation: Department of Oral Biology, School of Dentistry, Creighton University, Omaha, NE 68178, USA.
authors.forename: D Roselyn
authors.initials: DR
authors.lastname: Cerutis
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Dreyer
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Vierra
authors.forename: Joshua P
authors.initials: JP
authors.lastname: King
authors.forename: David J
authors.initials: DJ
authors.lastname: Wagner
authors.forename: Jacob L
authors.initials: JL
authors.lastname: Fimple
authors.forename: Franco
authors.initials: F
authors.lastname: Cordini
authors.forename: Timothy P
authors.initials: TP
authors.lastname: McVaney
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Parrish
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Wilwerding
authors.forename: John S
authors.initials: JS
authors.lastname: Mattson
mesh_terms: D000704:Analysis of Variance; D000077214:Becaplermin; D018929:Cell Culture Techniques / Q000379:methods; D002633:Chemotaxis / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008964:Molar, Third; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D049368:Receptors, Lysophosphatidic Acid / Q000032:analysis; D014945:Wound Healing / Q000502:physiology*
chemical_list: D008246:Lysophospholipids; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D049368:Receptors, Lysophosphatidic Acid; D000077214:Becaplermin; D004247:DNA; D048052:Mitogen-Activated Protein Kinase 3; C032881:lysophosphatidic acid