title: Effect of neurotrophin-4/5 on bone/cementum-related protein expressions and DNA synthesis in cultures of human periodontal ligament cells.
abstract: BACKGROUND
  We studied neurotrophins (NTs) as signaling molecules for periodontal tissue regeneration and showed that nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) modulate the proliferation and differentiation of human periodontal ligament (HPL) cells in vitro. The purpose of this study was to investigate whether NT-4/5 also has the ability to regulate the function of HPL cells.
  
  
  METHODS
  mRNA expressions of NT-4/5 and its high-affinity tyrosine kinase receptor (trk)B were analyzed in HPL cells by reverse transcription-polymerase chain reaction. We examined how NT-4/5 regulates the mRNA expression of bone/cementum-related proteins (alkaline phosphatase [ALPase], osteopontin [OPN], osteocalcin [OC], and bone morphogenetic protein [BMP]-2) in cultures of HPL cells. Moreover, the effects of NT-4/5 on calcification, the production of OPN and OC, and DNA synthesis in HPL cells were examined.
  
  
  RESULTS
  NT-4/5 and trkB mRNA were expressed in HPL cells. NT-4/5 elevated the mRNA levels of ALPase, OPN, OC, and BMP-2 and the syntheses of OPN, OC, and DNA in HPL cells. PD98059, an extracellular signal-regulated kinase (ERK) inhibitor, obviated the increase in the mRNA levels of ALPase, OPN, OC, and BMP-2. NT-4/5 increased the levels of phosphorylated ERK1/2. Furthermore, NT-4/5 enhanced the amount of mineral deposits in cultures of HPL cells.
  
  
  CONCLUSIONS
  NT-4/5, as well as BDNF and NGF, is suggested to play a role in the regulation of function of periodontal ligament cells.
authors.affiliation: Department of Periodontal Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. mizuno@hiroshima-u.ac.jp
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Mizuno
authors.forename: Hideki
authors.initials: H
authors.lastname: Shiba
authors.forename: Takafumi
authors.initials: T
authors.lastname: Inui
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Takeda
authors.forename: Mikihito
authors.initials: M
authors.lastname: Kajiya
authors.forename: Naohiko
authors.initials: N
authors.lastname: Hasegawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Hidemi
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D003739:Dental Cementum / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D053495:Osteopontin / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D055396:Bone Morphogenetic Protein 2; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D053495:Osteopontin; C071951:neurotrophin 5; D004247:DNA; D020813:Receptor, trkB; D048049:Extracellular Signal-Regulated MAP Kinases; D000469:Alkaline Phosphatase; C073922:neurotrophin 4