title: Collagen Type IV and Laminin Expressions during Cartilage Repair and in Late Clinically Failed Repair Tissues from Human Subjects.
abstract: OBJECTIVE
  To identify the collagen type IV (Col4) isoform in articular cartilage and to evaluate the expressions of Col4 and laminin in the pericellular matrix (PCM) in damaged cartilage and during cartilage repair.
  
  
  METHODS
  The Col4 isoform was determined in chondrocytes isolated from 6 patients cultured up to 6 days and in 21% O2 or 1% O2, and the gene expression of Col4 α-chains was investigated. The distribution of Col4 and laminin in traumatically damaged cartilage (n = 7) and clinically failed cartilage repair (microfracture, TruFit, autologous chondrocyte implantation; n = 11) were investigated using immunohistochemistry. Normal human cartilage was used as control (n = 8). The distribution during clinical cartilage repair procedures was investigated in a minipig model with 6-month follow-up (untreated chondral, untreated osteochondral, microfracture, autologous chondrocyte implantation; n = 10).
  
  
  RESULTS
  The Col4 isoform in articular cartilage was characterized as α1α1α2, which is an isoform containing antiangiogenic domains in the NC1-terminals (arresten and canstatin). In normal cartilage, laminin and Col4 was exclusively found in the PCM. High amounts (>50%) of Col4 in the PCM significantly decreased in damaged cartilage (P = 0.004) and clinically failed repair tissue (P < 0.001). Laminin was only found with high expression (>50%) in 4/8 of the normal samples, which was not statistically significantly different from damaged cartilage (P = 0.15) or failed cartilage repair (P = 0.054).
  
  
  CONCLUSIONS
  Col4 in cartilage contain antiangiogenic domains and may play a role in the hypoxic environment in articular cartilage. Col4 and laminin was not found in the PCM of damaged and clinically failed repair.
authors.affiliation: Department of Orthopedics, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA; Tissue Engineering Labs, VA Boston Healthcare System, Boston, MA, USA; Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Casper Bindzus
authors.initials: CB
authors.lastname: Foldager
authors.affiliation: Department of Orthopedics, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA; Tissue Engineering Labs, VA Boston Healthcare System, Boston, MA, USA; Discipline of Oral Sciences, Faculty of Dentistry, National University of Singapore, Singapore.
authors.forename: Wei Seong
authors.initials: WS
authors.lastname: Toh
authors.affiliation: Orthopaedic Research Laboratory, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Bjørn Borsøe
authors.initials: BB
authors.lastname: Christensen
authors.affiliation: Sports Trauma Clinic, Department of Orthopaedics, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Lind
authors.affiliation: Cartilage Repair Center, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Gomoll
authors.affiliation: Department of Orthopedics, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA; Tissue Engineering Labs, VA Boston Healthcare System, Boston, MA, USA.
authors.forename: Myron
authors.initials: M
authors.lastname: Spector
keywords: articular cartilage; cartilage repair; collagen type IV; laminin