title: Mechanical stress-induced apoptosis of nucleus pulposus cells: an in vitro and in vivo rat model.
abstract: BACKGROUND
  Un-physiological loads play an important role in the degenerative process of inter-vertebral discs (IVD). In this study, we used an in vitro and in vivo rat model to investigate the mechanism of nucleus pulposus (NP) cells apoptosis induced by mechanical stress.
  
  
  METHODS
  Static compressive load to IVDs of rat tails was used as the in vivo model. For the in vitro model, NP cells were tested under the physiological and un-physiological loading. For histological examination, apoptotic index study, and apoptotic gene expression, we also selected cytokines [bone morphogenetic protein (BMP)-2/7, insulin-like growth factor (IGF)-1, platelet-derived growth factor (PDGF)] to be analyzed.
  
  
  RESULTS
  Under mechanical loading, cellular density was significantly decreased, but there was an increase of TUNEL positive cells and apoptosis index. In a dose-dependent manner; the necrosis became apparent in the un-physiologic strain. The selected cytokines (BMP-2/7, IGF-1, PDGF) can significantly reduce the percentage of apoptotic and necrotic cells.
  
  
  CONCLUSIONS
  We conclude that the intrinsic (mitochondrial) apoptotic pathway plays an important role in the compressive load-induced apoptosis of NP cells. Combination therapy reducing the mechanical load and selected cytokines (BMP-2/7, IGF-1 and PDGF) may have considerable promise in the treatment of spine disc degeneration.
authors: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors: Yi-Jie
authors: YJ
authors: Kuo
authors: Graduate Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan, ROC.
authors: Lien-Chen
authors: LC
authors: Wu
authors: Department of Orthopedic Surgery, School of Medicine, College of Medicine, National Taiwan University, 1, Jen-Ai Road, Section 1, Taipei 10051, Taiwan, ROC; Department of Orthopedic Surgery, National Taiwan University Hospital Hsin-Chu Branch, No.25, Lane 442, Sec. 1, Jingguo Rd., Hsinchu City 30059, Taiwan, ROC. Electronic address: drjssun@gmail.com.
authors: Jui-Sheng
authors: JS
authors: Sun
authors: Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu City, Taiwan, ROC.
authors: Ming-Hong
authors: MH
authors: Chen
authors: Department of Biology, Western University, London, ON N6A 5C1, Canada.
authors: Man-Ger
authors: MG
authors: Sun
authors: Department of Orthopedic Surgery, Taipei Medical University-Shuang-Ho Hospital, No.291, Jhongjheng Rd., Jhonghe City, New Taipei 23561, Taiwan, ROC. Electronic address: tsuangyh@gmail.com.
authors: Yang-Hwei
authors: YH
authors: Tsuang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D005434:Flow Cytometry; D050815:Fractures, Compression / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D012313:RNA / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013314:Stress, Mechanical; D013623:Tail / Q000293:injuries* / Q000473:pathology
chemical_list: D055396:Bone Morphogenetic Protein 2; D016207:Cytokines; D012313:RNA