title: The Transient Chondrocyte Phenotype in Human Osteophytic Cartilage: A Role of Pigment Epithelium-Derived Factor?
abstract: OBJECTIVE
  To identify factors that are responsible for the phenotypic differences between transient chondrocytes within human osteophytes prone to endochondral ossification and permanent chondrocytes within articular cartilage persisting for decades.
  
  
  METHODS
  Differential gene expression of chondrocytes from human osteophytes or from articular cartilage was detected by cDNA microarray analysis. The expression of pigment epithelium-derived factor (PEDF), one of the most impressively differentially expressed genes, was validated by quantitative reverse transcriptase polymerase chain reaction as well as immunohistochemistry. The mode of action of PEDF was explored by cell viability assays and by detecting target genes.
  
  
  RESULTS
  PEDF mRNA expression was upregulated by 118.5-fold (P = 0.01) in human osteophytic cartilage compared with articular cartilage, which was reflected by strong immunostaining for PEDF in the cartilaginous layer of osteophytes but largely negative staining in articular cartilage. Elevated levels of PEDF in osteophytes were associated with enhanced apoptosis. PEDF increased the expression of the proapoptotic factor FasL and induced cell death in cell culture. Osteochondral progenitor cells were more responsive to PEDF than differentiated articular chondrocytes.
  
  
  CONCLUSIONS
  The induction of the proapoptotic factor PEDF within the osteophyte cartilage suggests a molecular concept for the transient chondrocyte phenotype that arises from progenitor cells and is prone to terminal differentiation and cell death.
authors.affiliation: Department of Orthopaedic Trauma Surgery, University Hospital Erlangen, Erlangen, Germany ; Department of Orthopaedic Rheumatology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Klinger
authors.affiliation: Department of Internal Medicine III and Institute for Clinical Immunology, University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Beyer
authors.affiliation: Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Arif B
authors.initials: AB
authors.lastname: Ekici
authors.affiliation: Department of Orthopaedic Rheumatology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Carl
authors.affiliation: Department of Internal Medicine III and Institute for Clinical Immunology, University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.affiliation: Department of Orthopaedic Rheumatology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Swoboda
authors.affiliation: Department of Orthopaedic Trauma Surgery, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Friedrich F
authors.initials: FF
authors.lastname: Hennig
authors.affiliation: Department of Orthopaedic Trauma Surgery, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Kolja
authors.initials: K
authors.lastname: Gelse
keywords: PEDF; osteoarthritis; osteophyte; transient chondrocyte phenotype