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Effects of rAAV-Mediated sox9 Overexpression on the Biological Activities of Human Osteoarthritic Articular Chondrocytes in Their Intrinsic Three-Dimensional Environment
dc.contributor.author | Daniels, Oliver | |
dc.contributor.author | Rey-Rico, Ana | |
dc.contributor.author | Schmitt, Gertrud | |
dc.contributor.author | Venkatesan, Jagadeesh Kumar | |
dc.contributor.author | Cucchiarini, Magali | |
dc.contributor.author | Frisch, Janina | |
dc.date.accessioned | 2024-07-10T15:30:58Z | |
dc.date.available | 2024-07-10T15:30:58Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | Daniels, O.; Frisch, J.; Venkatesan, J.K.; Rey-Rico, A.; Schmitt, G.; Cucchiarini, M. Effects of rAAV-Mediated sox9 Overexpression on the Biological Activities of Human Osteoarthritic Articular Chondrocytes in Their Intrinsic Three-Dimensional Environment. J. Clin. Med. 2019, 8, 1637. https://doi.org/10.3390/jcm8101637 | es_ES |
dc.identifier.uri | http://hdl.handle.net/2183/37895 | |
dc.description.abstract | [Abstract] Gene therapy for osteoarthritis offers powerful, long-lasting tools that are well adapted to treat such a slow, progressive disorder, especially those therapies based on the clinically adapted recombinant adeno-associated viral (rAAV) vectors. Here, we examined the ability of an rAAV construct carrying a therapeutic sequence for the cartilage-specific SOX9 transcription factor to modulate the phenotype of human osteoarthritic articular chondrocytes compared with normal chondrocytes in a three-dimensional environment where the cells are embedded in their extracellular matrix. Successful sox9 overexpression via rAAV was noted for at least 21 days, leading to the significant production of major matrix components (proteoglycans, type-II collagen) without affecting the proliferation of the cells, while the cells contained premature hypertrophic processes relative to control conditions (reporter rAAV-lacZ application, absence of vector treatment). These findings show the value of using rAAV to adjust the osteoarthritic phenotype when the chondrocytes are confined in their inherently altered environment and the possibility of impacting key cellular processes via gene therapy to remodel human osteoarthritic cartilage lesions. | es_ES |
dc.description.sponsorship | This research was funded by the German Osteoarthritis Foundation (Deutsche Arthrose-Hilfe e.V.). This research was funded by the German Osteoarthritis Foundation (Deutsche Arthrose-Hilfe e.V.). The authors thank R. J. Samulski (The Gene Therapy Center, University of North Carolina, Chapel Hill, NC), X. Xiao (The Gene Therapy Center, University of Pittsburgh, Pittsburgh, PA), and E. F. Terwilliger (Division of Experimental Medicine, Harvard Institutes of Medicine and Beth Israel Deaconess Medical Center, Boston, MA) for providing the genomic AAV-2 plasmid clones, the packaging plasmid pXX2, the Adenovirus helper plasmid pXX6, and the 293 cell line, and G. Scherer (Institute for Human Genetics and Anthropology, Albert-Ludwig University, Freiburg, Germany) for the human sox9 cDNA. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.relation.uri | https://doi.org/10.3390/jcm8101637 | es_ES |
dc.rights | Creative Commons Attribution (CC BY) license 4.0 | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | Cartilage repair | es_ES |
dc.subject | Osteoarthritis | es_ES |
dc.subject | RAAV | es_ES |
dc.subject | SOX9 | es_ES |
dc.subject | Chondrocyte phenotype | es_ES |
dc.title | Effects of rAAV-Mediated sox9 Overexpression on the Biological Activities of Human Osteoarthritic Articular Chondrocytes in Their Intrinsic Three-Dimensional Environment | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.access | info:eu-repo/semantics/openAccess | es_ES |
UDC.journalTitle | Journal of Clinical Medicine | es_ES |
UDC.volume | 8 | es_ES |
UDC.issue | 10 | es_ES |
UDC.startPage | 1637 | es_ES |
dc.identifier.doi | 10.3390/jcm8101637 |