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Titel: Restoration of the extracellular matrix in human osteoarthritic articular cartilage by overexpression of the transcription factor SOX9
Verfasser: Cucchiarini, Magali
Thurn, Tanja
Weimer, Anja
Kohn, Dieter
Terwilliger, Ernest F.
Madry, Henning
Sprache: Deutsch
Erscheinungsjahr: 2007
Quelle: Arthritis & rheumatism. - 56. 2007, 1, 158-167
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumentart : Journalartikel
Kurzfassung: Objective. Human osteoarthritis (OA) is characterized by a pathologic shift in articular cartilage homeostasis toward the progressive loss of extracellular matrix (ECM). The purpose of this study was to investigate the ability of rAAV-mediated SOX9 overexpression to restore major ECM components in human OA articular cartilage. Methods. We monitored the synthesis and content of proteoglycans and type II collagen in 3-dimensional cultures of human normal and OA articular chondrocytes and in explant cultures of human normal and OA articular cartilage following direct application of a recombinant adeno-associated virus (rAAV) SOX9 vector in vitro and in situ. We also analyzed the effects of this treatment on cell proliferation in these systems. Results. Following SOX9 gene transfer, expression levels of proteoglycans and type II collagen increased over time in normal and OA articular chondrocytes in vitro. In situ, overexpression of SOX9 in normal and OA articular cartilage stimulated proteoglycan and type II collagen synthesis in a dose-dependent manner. These effects were not associated with changes in chondrocyte proliferation. Notably, expression of the 2 principal matrix components could be restored in OA articular cartilage to levels similar to those in normal cartilage. Conclusion. These data support the concept of using direct, rAAV-mediated transfer of chondrogenic genes to articular cartilage for the treatment of OA in humans.
Link zu diesem Datensatz: urn:nbn:de:bsz:291-scidok-14956
hdl:20.500.11880/21032
http://dx.doi.org/10.22028/D291-20976
SciDok-Publikation: 21-Apr-2008
Fakultät: Fakultät 2 - Medizin
Fachrichtung: M - Orthopädie
Fakultät / Institution:M - Medizinische Fakultät

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