Please use this identifier to cite or link to this item: doi:10.22028/D291-20976
Title: Restoration of the extracellular matrix in human osteoarthritic articular cartilage by overexpression of the transcription factor SOX9
Author(s): Cucchiarini, Magali
Thurn, Tanja
Weimer, Anja
Kohn, Dieter
Terwilliger, Ernest F.
Madry, Henning
Language: German
Year of Publication: 2007
OPUS Source: Arthritis & rheumatism. - 56. 2007, 1, 158-167
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: 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 to this record: urn:nbn:de:bsz:291-scidok-14956
Date of registration: 21-Apr-2008
Faculty: M - Medizinische Fakultät
Department: M - Orthopädie
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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