title: Effect of low-intensity pulsed ultrasound on bone morphogenetic protein 7-induced osteogenic differentiation of human nonunion tissue-derived cells in vitro.
abstract: OBJECTIVE
  Low-intensity pulsed ultrasound (US) has been shown to have positive effects on the healing of nonunions, and bone morphogenetic protein 7 (BMP-7) is known to be a strong stimulator of osteogenic differentiation. Recently, we showed that nonunion tissue contains multilineage mesenchymal progenitor cells, suggesting that nonunion tissue-derived cells may play an important role during the healing process of nonunions. In this study, we investigated whether low-intensity pulsed US promoted BMP-7-induced osteogenic differentiation of nonunion tissue-derived cells in vitro.
  
  
  METHODS
  Nonunion tissue-derived cells were isolated from 7 patients. The cells were divided into two groups: (1) BMP-7 alone, consisting of nonunion tissue-derived cells cultured in osteogenic medium containing BMP-7 without low-intensity pulsed US treatment; and (2) BMP-7 + low-intensity pulsed US, consisting of nonunion tissue-derived cells cultured in osteogenic medium containing BMP-7 with low-intensity pulsed US treatment. The osteogenic differentiation potential and proliferation of nonunion tissue-derived cells were compared between the two groups.
  
  
  RESULTS
  The alkaline phosphatase activity, gene expression levels of alkaline phosphatase and runt-related transcription factor 2, and mineralization were higher in the BMP-7 + low-intensity pulsed US group than in the BMP-7-alone group. There was no significant difference in cell proliferation between the two groups.
  
  
  CONCLUSIONS
  These findings show a significant effect of low-intensity pulsed US on the osteogenic differentiation of nonunion tissue-derived cells induced by BMP-7. This study may provide substantial evidence for the clinical combined application of BMP-7 and low-intensity pulsed US for nonunion treatment.
authors.affiliation: Department of Orthopedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. tni
authors.forename: Takaaki
authors.initials: T
authors.lastname: Koga
authors.forename: Sang Yang
authors.initials: SY
authors.lastname: Lee
authors.forename: Takahiro
authors.initials: T
authors.lastname: Niikura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Koh
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Dogaki
authors.forename: Etsuko
authors.initials: E
authors.lastname: Okumachi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akisue
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kuroda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
mesh_terms: D055419:Bone Morphogenetic Protein 7 / Q000008:administration & dosage*; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D017759:Fractures, Malunited / Q000473:pathology* / Q000628:therapy; D019220:High-Energy Shock Waves; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D010012:Osteogenesis / Q000187:drug effects* / Q000528:radiation effects*; D011829:Radiation Dosage; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D055419:Bone Morphogenetic Protein 7
keywords: bone morphogenetic protein 7; low-intensity pulsed ultrasound; nonunion; osteogenic differentiation