title: Intermittent cyclic mechanical tension promotes endplate cartilage degeneration via canonical Wnt signaling pathway and E-cadherin/β-catenin complex cross-talk.
abstract: OBJECTIVE
  This study aimed to investigate the role of the Wnt/β-catenin signaling pathway and E-cadherin/β-catenin complex in intermittent cyclic mechanical tension (ICMT)-induced endplate cartilage degeneration.
  
  
  METHODS
  β-Catenin expression was measured in disc samples obtained from patients with disc degeneration and those with cervical vertebrae fracture or dislocation. Histological staining was performed to examine the disc tissue morphology and extracellular matrix after application of ICMT in vitro and in vivo. Multiple strategies were employed to examine activation of Wnt/β-catenin signaling after ICMT application in vivo and in vitro. Co-immunoprecipitation was performed to examine the interaction between E-cadherin and β-catenin. Pathway-specific inhibitors and an E-cadherin expression plasmid were used to regulate Wnt/β-catenin signaling and E-cadherin expression.
  
  
  RESULTS
  β-Catenin protein expression was elevated significantly, whereas cartilaginous genes were down-regulated in endplate cartilage samples obtained from patients with disc degeneration. ICMT loading led to Wnt/β-catenin signaling activation and the loss of the chondrogenic phenotype of endplate chondrocytes in both an in vivo rabbit model and in vitro endplate chondrocyte culture system. Inhibition of Wnt/β-catenin signaling suppressed the decrease in ICMT-induced cartilaginous gene expression. Furthermore, E-cadherin expression was inhibited by ICMT stimulation, resulting in a decrease in the interaction between E-cadherin and β-catenin proteins. Over-expression of E-cadherin rescued the cartilaginous gene expression by enhancing the interaction between E-cadherin and β-catenin proteins.
  
  
  CONCLUSIONS
  ICMT promotes endplate cartilage degeneration via activation of Wnt/β-catenin signaling and suppression of physical protein-protein interactions between E-cadherin and β-catenin.
authors.affiliation: Department of Orthopedic Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, 241001, Anhui, China. Electronic address: xuhg@medmail.com.cn.
authors.forename: H-g
authors.initials: HG
authors.lastname: Xu
authors.affiliation: Department of Orthopedic Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, 241001, Anhui, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Department of Orthopedic Surgery, Chinese Medicine Hospitals of Wuhu, Wuhu, 241001, Anhui, China.
authors.forename: J-x
authors.initials: JX
authors.lastname: Song
authors.affiliation: Department of Cell Biology and Genetics, Zunyi Medical College, Zunyi, 563003, Guizhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, 241001, Anhui, China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, 241001, Anhui, China.
authors.forename: P
authors.initials: P
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China.
authors.forename: C-d
authors.initials: CD
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China. Electronic address: xlzhang@sibs.ac.cn.
authors.forename: X-l
authors.initials: XL
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism*; D016022:Case-Control Studies; D002574:Cervical Vertebrae / Q000293:injuries; D019902:Chondrocytes / Q000378:metabolism*; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011312:Pressure; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016103:Spinal Fractures; D013314:Stress, Mechanical; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D015820:Cadherins; D051153:Wnt Proteins; D051176:beta Catenin
keywords: Degeneration; E-cadherin; Endplate cartilage; Mechanical tension; β-catenin