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doi:10.22028/D291-44048
Title: | In vivo rAAV-mediated human TGF-β overexpression reduces perifocal osteoarthritis and improves osteochondral repair in a large animal model at one year |
Author(s): | Schrenker, S. Cucchiarini, M. Goebel, L. Oláh, T. Venkatesan, J.K. Schmitt, G. Speicher-Mentges, S. Maihöfer, J. Gao, L. Zurakowski, D. Menger, M. D. Laschke, M. W. Madry, H. |
Language: | English |
Title: | Osteoarthritis and Cartilage |
Volume: | 31 (2023) |
Issue: | 4 |
Pages: | 467-481 |
Publisher/Platform: | Elsevier |
Year of Publication: | 2022 |
Free key words: | Osteochondral defects Osteoarthritis rAAV TGF-b Large animal model Cartilage repair |
DDC notations: | 610 Medicine and health |
Publikation type: | Journal Article |
Abstract: | Objective: Osteoarthritis (OA) is a serious consequence of focal osteochondral defects. Gene transfer of human transforming growth factor beta (hTGF-b) with recombinant adeno-associated virus (rAAV) vectors offers a strategy to improve osteochondral repair. However, the long-term in vivo effects of such rAAV-mediated TGF-b overexpression including its potential benefits on OA development remain unknown. Method: Focal osteochondral defects in minipig knees received rAAV-lacZ (control) or rAAV-hTGF-b in vivo. After one year, osteochondral repair and perifocal OA were visualized using validated macroscopic scoring, ultra-high-field MRI at 9.4 T, and micro-CT. A quantitative estimation of the cellular densities and a validated semi-quantitative scoring of histological and immunohistological parameters completed the analysis of microarchitectural parameters. Results: Direct rAAV-hTGF-b application induced and maintained significantly improved defect filling and safranin O staining intensity and overall cartilage repair at one year in vivo. In addition, rAAV-hTGF-b led to significantly higher chondrocyte densities within the cartilaginous repair tissue without affecting chondrocyte hypertrophy and minimized subarticular trabecular separation. Of note, rAAV-hTGF-b significantly improved the adjacent cartilage structure and chondrocyte density and reduced overall perifocal OA development after one year in vivo. Conclusions: rAAV-hTGF-b treatment improves long-term osteochondral repair and delays the progression of perifocal OA in a translational model. These findings have considerable potential for targeted molecular approaches to treat focal osteochondral defects. |
DOI of the first publication: | 10.1016/j.joca.2022.11.010 |
URL of the first publication: | https://doi.org/10.1016/j.joca.2022.11.010 |
Link to this record: | urn:nbn:de:bsz:291--ds-440489 hdl:20.500.11880/39405 http://dx.doi.org/10.22028/D291-44048 |
ISSN: | 1063-4584 |
Date of registration: | 20-Jan-2025 |
Description of the related object: | Supplementary data |
Related object: | https://ars.els-cdn.com/content/image/1-s2.0-S1063458422009372-mmc1.docx |
Faculty: | M - Medizinische Fakultät |
Department: | M - Chirurgie M - Orthopädie |
Professorship: | M - Prof. Dr. Henning Madry M - Prof. Dr. Michael D. Menger |
Collections: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
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