title: Laminins and Nidogens in the Pericellular Matrix of Chondrocytes: Their Role in Osteoarthritis and Chondrogenic Differentiation.
abstract: The aim of this study was to investigate the role of laminins and nidogen-2 in osteoarthritis (OA) and their potential to support chondrogenic differentiation. We applied immunohistochemistry, electron microscopy, siRNA, quantitative RT-PCR, Western blot, and proteome analysis for the investigation of cartilage tissue and isolated chondrocytes in three-dimensional culture obtained from patients with late-stage knee OA and nidogen-2 knockout mice. We demonstrate that subunits of laminins appear in OA cartilage and that nidogen-2-null mice exhibit typical osteoarthritic features. Chondrogenic progenitor cells (CPCs) produced high levels of laminin-α1, laminin-α5, and nidogen-2 in their pericellular matrix, and laminin-α1 enhanced collagen type II and reduced collagen type I expression by cultured CPCs. Nidogen-2 increased SOX9 gene expression. Knockdown of nidogen-2 reduced SOX9 expression, whereas it up-regulated RUNX2 expression. This study reveals that the influence of the pericellular matrix on CPCs is important for the expression of the major regulator transcription factors, SOX9 and RUNX2. Our novel findings that laminins and nidogen-2 drive CPCs toward chondrogenesis may help in the elucidation of new treatment strategies for cartilage tissue regeneration.
authors.affiliation: Department of Prosthodontics, Tissue Regeneration Work Group, Georg August University, Göttingen, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Schminke
authors.affiliation: Clinic of Nephrology and Rheumatology, Georg August University, Göttingen, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Frese
authors.affiliation: Department of Prosthodontics, Tissue Regeneration Work Group, Georg August University, Göttingen, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Bode
authors.affiliation: Tissue Engineering, Regeneration, and Repair Program, Hospital for Special Surgery, Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Goldring
authors.affiliation: Department of Prosthodontics, Tissue Regeneration Work Group, Georg August University, Göttingen, Germany. Electronic address: nmiosge@gwdg.de.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Miosge
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D019902:Chondrocytes / Q000378:metabolism*; D020219:Chondrogenesis / Q000502:physiology; D024043:Collagen Type II / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D024043:Collagen Type II; D007797:Laminin; C114729:NID2 protein, human