title: PEDF Is Associated with the Termination of Chondrocyte Phenotype and Catabolism of Cartilage Tissue.
abstract: Objective.To investigate the expression and target genes of pigment epithelium-derived factor (PEDF) in cartilage and chondrocytes, respectively.Methods.We analyzed the expression pattern of PEDF in different human cartilaginous tissues including articular cartilage, osteophytic cartilage, and fetal epiphyseal and growth plate cartilage, by immunohistochemistry and quantitative real-time (qRT) PCR. Transcriptome analysis after stimulation of human articular chondrocytes with rhPEDF was performed by RNA sequencing (RNA-Seq) and confirmed by qRT-PCR.Results.Immunohistochemically, PEDF could be detected in transient cartilaginous tissue that is prone to undergo endochondral ossification, including epiphyseal cartilage, growth plate cartilage, and osteophytic cartilage. In contrast, PEDF was hardly detected in healthy articular cartilage and in the superficial zone of epiphyses, regions that are characterized by a permanent stable chondrocyte phenotype. RNA-Seq analysis and qRT-PCR demonstrated that rhPEDF significantly induced the expression of a number of matrix-degrading factors including SAA1, MMP1, MMP3, and MMP13. Simultaneously, a number of cartilage-specific genes including COL2A1, COL9A2, COMP, and LECT were among the most significantly downregulated genes.Conclusions.PEDF represents a marker for transient cartilage during all neonatal and postnatal developmental stages and promotes the termination of cartilage tissue by upregulation of matrix-degrading factors and downregulation of cartilage-specific genes. These data provide the basis for novel strategies to stabilize the phenotype of articular cartilage and prevent its degradation.
authors.affiliation: Department of Orthopaedic and Trauma Surgery, University Hospital Erlangen, Erlangen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Klinger
authors.affiliation: Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: S
authors.identifier: 0000-0001-7045-6327
authors.initials: S
authors.lastname: Lukassen
authors.affiliation: Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Ferrazzi
authors.affiliation: Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: A B
authors.identifier: 0000-0001-6099-7066
authors.initials: AB
authors.lastname: Ekici
authors.affiliation: Division of Orthopaedic Rheumatology, Department of Orthopaedics, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Hotfiel
authors.affiliation: Division of Orthopaedic Rheumatology, Department of Orthopaedics, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Swoboda
authors.affiliation: Department of Pathology, Medical Center Coburg, Coburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Aigner
authors.affiliation: Department of Orthopaedic and Trauma Surgery, University Hospital Erlangen, Erlangen, Germany.
authors.forename: K
authors.identifier: 0000-0002-3349-9325
authors.initials: K
authors.lastname: Gelse
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002356:Cartilage / Q000378:metabolism* / Q000473:pathology*; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology*; D004838:Epiphyses / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006132:Growth Plate / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007596:Joints / Q000378:metabolism / Q000473:pathology; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D054850:Osteophyte / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor