Please use this identifier to cite or link to this item: doi:10.22028/D291-44048
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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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