title: Intermittent Cyclic Mechanical Tension Promotes Degeneration of Endplate Cartilage via the Nuclear Factor-κB Signaling Pathway: an in Vivo Study.
abstract: OBJECTIVE
  To establish a rabbit model for investigating the effects of intermittent cyclic mechanical tension (ICMT) on promoting degeneration of endplate cartilage.
  
  
  METHODS
  Forty New Zealand white rabbits were subjected to surgery and randomly divided into three equal groups as follows: control group (no treatment, n = 10), sham group (animals underwent a sham operation but were not subjected to mechanical tensile strain, n = 15) and loaded group (discs were subjected to 1.5 MPa external tensile loading by using an external loading device during the animals' daily activity, n = 15). Mechanical tensile strain was applied for 8 h/d. The animals were examined radiologically after 8 weeks treatment and then killed for removal of endplate cartilage tissue samples from their spines. Histological staining was performed to examine the morphology of endplate cartilage tissue. Multiple strategies were employed to examine degeneration of endplate cartilage and nuclear factor (NF)-κB signaling pathway activation.
  
  
  RESULTS
  After ICMT loading for 56 days, radiology revealed ossification, hyperosteogeny and stenosis in the intervertebral spaces. Examination of hematoxylin and eosin staining of sections of endplate cartilage showed significant damage as the load duration increased in the ICMT loading group. Expression of aggrecan (ACAN), type II collagen (COL-2A), SRY-related high mobility group-box gene 9 (SOX9) was down-regulated (FACAN = 21.515, P < 0.01; FCOL-2A = 6.670, P = 0.05; FSOX9 = 7.888, P < 0.05), whereas that of matrix metallopeptidase 13 (MMP13) was up-regulated (FMMP13 = 14.120, P < 0.01) after ICMT. Western blot and immunofluorescence revealed that expression of protein was consistent with gene expression results. Additionally, ICMT loading can lead to NF-κB signaling pathway activation as well as degeneration of endplate cartilage.
  
  
  CONCLUSIONS
  These experiments indicate that ICMT contributes to the activation of NF-κB signaling pathway in vivo and that the NF-κB signaling pathway further up-regulates MMP13, leading to degeneration of endplate cartilage.
authors.affiliation: Department of Orthopaedic Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Orthopaedic Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, China. xlllan2012@126.com.
authors.forename: Hong-Guang
authors.initials: HG
authors.lastname: Xu
authors.affiliation: Department of Orthopaedic Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Orthopaedic Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, China.
authors.forename: Yong-Ming
authors.initials: YM
authors.lastname: Xu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001696:Biomechanical Phenomena; D015153:Blotting, Western; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D011817:Rabbits; D011859:Radiography; D011897:Random Allocation; D015398:Signal Transduction; D013312:Stress, Physiological / Q000502:physiology*; D015854:Up-Regulation; D016474:Weight-Bearing
chemical_list: D015415:Biomarkers; D016328:NF-kappa B
keywords: Endplate cartilage degeneration; In vivo; Intermittent cyclic mechanical tension; NF-κF signaling pathway