title: Expressions of membrane-type I matrix metalloproteinase, Ki-67 protein, and type II collagen by chondrocytes migrating from cartilage endplate into nucleus pulposus in rat intervertebral discs: a cartilage endplate-fracture model using an intervertebral disc organ culture.
abstract: METHODS
  Immunohistochemistry was performed in organ-cultured intact and cartilage endplate (CE)-fractured rat intervertebral discs (IVDs).
  
  
  OBJECTIVE
  To demonstrate biologic events associated with migration of chondrocytes from hyaline CE into nucleus pulposus (NP).
  
  
  BACKGROUND
  It was recently revealed that the transition from a notochordal NP to a fibrocartilaginous NP in the rabbit IVD is accomplished exogenously by chondrocytes migrating from CEs into the NP. This observation has not been studied in other animal models, and the biologic events associated with chondrocyte migration have not been elucidated in the literature.
  
  
  METHODS
  IVDs including cranial and caudal CEs were obtained from 4-week, 6-month, 12-month, and 18-month old Wistar rats. To accelerate chondrocyte migration, CEs of IVDs were fractured and cultured for 48 hours. IVDs without CE-fracture were used as a control for each age group. Expressions of membrane-type I matrix metalloproteinase (MT1-MMP, as a marker for cell migration and extracellular matrix digestion) and Ki-67 protein (as a proliferation marker) and pericellular deposition of type II collagen (as a marker for fibrocartilaginous matrix) by the chondrocytes migrating from CE into NP were examined immunohistochemically.
  
  
  RESULTS
  In the control groups, chondrocyte migration limited only along the periphery of the notochordal NP and no chondrocytes were inside the NP proper. However, all the IVDs in the CE-fracture groups showed direct and more extensive migration of chondrocytes from CEs into the NP proper. The migrating chondrocytes in both control and CE-fracture groups expressed MT1-MMP and Ki-67 protein and deposited type II collagen in the NP.
  
  
  CONCLUSIONS
  This report demonstrates the chondrocyte migration from CE into NP in the organ-cultured rat IVDs. This phenomenon is accelerated in the presence of CE fracture. The chondrocytes migrating from CEs into the NP expressed MT1-MMP and Ki-67 protein and deposited type II collagen. These biologic strategies probably enable chondrocytes of the hyaline CE to migrate into the ectopic NP region, replace notochordal cells, and change the notochordal tissue into fibrocartilage. These results suggest that similar biologic mechanisms may be involved in the natural transition from the notochordal NP to the fibrocartilaginous NP in other animal models, including human.
authors.affiliation: Department of Orthopedic Surgery, St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. kiwonk@lycos.co.kr
authors.forename: Ki-Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Kee-Yong
authors.initials: KY
authors.lastname: Ha
authors.forename: Jong-Beom
authors.initials: JB
authors.lastname: Park
authors.forename: Young-Kyun
authors.initials: YK
authors.lastname: Woo
authors.forename: Ha-Na
authors.initials: HN
authors.lastname: Chung
authors.forename: Howard S
authors.initials: HS
authors.lastname: An
mesh_terms: D000818:Animals; D002356:Cartilage / Q000166:cytology* / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism*; D019085:Fluorescent Antibody Technique, Direct; D006132:Growth Plate / Q000166:cytology* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007403:Intervertebral Disc / Q000166:cytology* / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism*; D008159:Lumbar Vertebrae; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats
chemical_list: D024043:Collagen Type II; D019394:Ki-67 Antigen; D020781:Matrix Metalloproteinase 1