title: Low-intensity pulsed ultrasound stimulates matrix metabolism of human annulus fibrosus cells mediated by transforming growth factor β1 and extracellular signal-regulated kinase pathway.
abstract: OBJECTIVE
  There are limited strategies to restore the damaged annulus fibrosus (AF) of the intervertebral disc. Low-intensity pulsed ultrasound (LIPUS) has positive effects on the proliferation of several types of cells and the repair of damage tissue in vivo. However, scientific evidence of therapeutic effects of LIPUS on AF cells remains limited. The purpose of this study is to evaluate the feasibility of applying LIPUS to the repair of the AF.
  
  
  METHODS
  We used an in vitro model of human AF cells subjected to LIPUS stimulation to examine its effects on cell proliferation and matrix metabolism. Cell viability, synthesis of collagen and glycosaminoglycan (GAG), expression of matrix metalloproteinases (MMPs) and transforming growth factor β1 and pathways involving mitogen-activated protein kinases (MAPKs) were investigated.
  
  
  RESULTS
  LIPUS significantly enhanced proliferation of AF cells after 5 days of treatment. LIPUS with an intensity of 0.5 W/cm(2) increased the collagen and GAG synthesis and decreased the expressions of MMP-1 and -3 of human AF cells. Real-time polymerase chain reactions and western blotting analysis revealed that LIPUS could increase transforming growth factor β1 (TGF-β1) and activate extracellular signal-regulated kinase (ERK) pathway. In addition, TGF-β receptor kinase inhibitor could suppress the ultrasound-induced alterations in cell viability and matrix metabolism.
  
  
  CONCLUSIONS
  The findings suggested that LIPUS could be useful as a physical stimulation of cell metabolism for the repair of the AF.
authors: Department of Internal Medicine, Far Eastern Memorial Hospital , Taipei , Taiwan .
authors: Mei-Hsiu
authors: MH
authors: Chen
authors: Jui-Sheng
authors: JS
authors: Sun
authors: Shao-Yu
authors: SY
authors: Liao
authors: Po-An
authors: PA
authors: Tai
authors: Tin-Chou
authors: TC
authors: Li
authors: Ming-Hong
authors: MH
authors: Chen
mesh_terms: D000328:Adult; D049109:Cell Proliferation / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D013131:Spine / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D000069453:Ultrasonic Waves; D055815:Young Adult
chemical_list: D053773:Transforming Growth Factor beta1; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Annulus fibrosus; TGF-β1; collagen; glycosaminoglycan; low-intensity pulsed ultrasound; matrix metalloproteinase