title: Low-level laser therapy stimulates mineralization via increased Runx2 expression and ERK phosphorylation in osteoblasts.
abstract: OBJECTIVE
  This study examined the effects of low-level laser therapy (LLLT) on osteoblasts via insulin-like growth factor I (IGF-I) signal transduction.
  
  
  BACKGROUND
  Because orthodontic treatment is usually accompanied by bone formation, if bone formation can be promoted, the treatment and retention periods will be shorter. Recently, we reported the stimulatory effects of LLLT on bone formation. It was dependent on increased IGF-I, which plays an essential role in the anabolic regulation of bone metabolism. However, the signal transduction of IGF-I stimulated by LLLT was not elucidated.
  
  
  METHODS
  Mouse osteoblastic MC3T3-E1 cells were cultured with or without LLLT (0.96-3.82 J/cm(2)), and the expression of IGF-I and Runt-related transcription factor 2 (Runx2) and the phosphorylation of extracellular-signal-regulated kinase (ERK) were determined by using real-time PCR and Western blot analysis.
  
  
  RESULTS
  LLLT at 1.91 J/cm(2) significantly increased the expression of IGF-I and Runx2 and of ERK phosphorylation. Cyclolignan picropodophyllin (PPP; an IGF-I receptor inhibitor) partly inhibited the LLLT-induced expression of these factors. Moreover, when conditioned medium from the LLLT (1.91 J/cm(2)) cells was added to the MC3T3-E1 culture, the calcium content in the mineralized nodules increased significantly. PPP or noggin [a bone morphogenetic protein (BMP) antagonist] partly inhibited the LLLT-induced change in calcium content, and the addition of both PPP and noggin inhibited most of the LLLT-induced change in calcium content.
  
  
  CONCLUSIONS
  These results suggest that LLLT stimulates in vitro mineralization through increased IGF-I and BMP production, through Runx2 expression and ERK phosphorylation in osteoblasts.
authors.affiliation: Department of Orthodontics, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kiyosaki
authors.forename: Narihiro
authors.initials: N
authors.lastname: Mitsui
authors.forename: Naoto
authors.initials: N
authors.lastname: Suzuki
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Shimizu
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002113:Calcification, Physiologic / Q000528:radiation effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D017077:Culture Media, Conditioned; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D028022:Low-Level Light Therapy; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism* / Q000502:physiology*; D010766:Phosphorylation / Q000528:radiation effects; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D017077:Culture Media, Conditioned; D007334:Insulin-Like Growth Factor I; D011494:Protein Kinases