title: Static Compression Induces ECM Remodeling and Integrin α2β1 Expression and Signaling in a Rat Tail Caudal Intervertebral Disc Degeneration Model.
abstract: METHODS
  A three-level rat tail caudal intervertebral disc (IVD) degeneration (IVDD) model was established to study effects of static compression on extracellular matrix (ECM) remodeling and integrin signaling in IVDs during IVDD.
  
  
  OBJECTIVE
  The aim of this study was to investigate the effect of compression force on ECM remodeling and integrin signaling in IVDs during IVDD.
  
  
  BACKGROUND
  Integrins sense mechanical environment alteration via binding to ECM ligands and trigger intracellular signaling for pathological ECM remodeling during IVDD. However, the role of compression force in ECM remodeling and integrin signaling during IVDD remains elusive.
  
  
  METHODS
  Compared with the classical one-level rat tail IVDD model that exerts axial stress on the 8th to 9th caudal vertebral bodies, a three-level model was established by using an Ilizarov-type apparatus to exert stress on the 7th to 10th caudal vertebral bodies in rat tails for four weeks. To exclude side effects from surgical stab injury on manipulated discs, intact coccygeal (Co) disc Co8-9 was analyzed.
  
  
  RESULTS
  In three-level IVDD model, significant degeneration of the Co8-9 disc was observed. Quantitative real-time polymerase chain reaction (qRT-PCR) showed elevated mRNA expression of collagen types I, III, and V; matrix metalloproteinases (MMPs) 2, 3, 9, 13, 14; and decreased mRNA expression of collagen type II in Co8-9 disc. Compression loading altered the expression of integrin α2β1 (upregulated) and α10β1 (downregulated) in NP cells, and activated integrin downstream signaling. By contrast, one-level model showed more severe disc degeneration and ECM remodeling. Integrin α1, α2, α11, and β1 were upregulated, whereas α10 was downregulated. Similar activation of integrin signaling was observed.
  
  
  CONCLUSIONS
  Static compression altered collagen and MMP expression, and promoted β1 integrin expression and signaling in IVD. Compared with one-level rat tail IVDD model, three-level model showed milder effects on disc degeneration, ECM remodeling, and integrin expression, suggesting one-level model might involve other causes that induce IVDD via mechanisms independent of compression force.
  
  
  METHODS
  N/A.
authors.affiliation: The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: ZhanJun
authors.initials: Z
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: YouDong
authors.initials: Y
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: ShiHui
authors.initials: S
authors.lastname: Wang
authors.affiliation: The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: MaoHua
authors.initials: M
authors.lastname: Cheng
authors.affiliation: The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: HongMei
authors.initials: H
authors.lastname: Kong
authors.affiliation: The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: ChunGuang
authors.initials: C
authors.lastname: Sun
authors.affiliation: The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.affiliation: The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: TongLei
authors.initials: T
authors.lastname: Chen
authors.affiliation: The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: QiRong
authors.initials: Q
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: JianFeng
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D038982:Integrin alpha2beta1 / Q000096:biosynthesis*; D016023:Integrins / Q000096:biosynthesis; D007403:Intervertebral Disc / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013314:Stress, Mechanical
chemical_list: D038982:Integrin alpha2beta1; D016023:Integrins; D012333:RNA, Messenger; D003094:Collagen; D020782:Matrix Metalloproteinases