Your browser doesn't support javascript.
loading
Locally Directed Recombinant Adeno- Associated Virus-Mediated IGF-1 Gene Therapy Enhances Osteochondral Repair and Counteracts Early Osteoarthritis In Vivo.
Peifer, Carolin; Oláh, Tamás; Venkatesan, Jagadeesh K; Goebel, Lars; Orth, Patrick; Schmitt, Gertrud; Zurakowski, David; Menger, Michael D; Laschke, Matthias W; Cucchiarini, Magali; Madry, Henning.
Afiliação
  • Peifer C; Center of Experimental Orthopaedics, Saarland University, Homburg/Saar, Germany.
  • Oláh T; Center of Experimental Orthopaedics, Saarland University, Homburg/Saar, Germany.
  • Venkatesan JK; Center of Experimental Orthopaedics, Saarland University, Homburg/Saar, Germany.
  • Goebel L; Center of Experimental Orthopaedics, Saarland University, Homburg/Saar, Germany.
  • Orth P; Center of Experimental Orthopaedics, Saarland University, Homburg/Saar, Germany.
  • Schmitt G; Center of Experimental Orthopaedics, Saarland University, Homburg/Saar, Germany.
  • Zurakowski D; Departments of Anesthesia and Surgery, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.
  • Menger MD; Institute for Clinical & Experimental Surgery, Saarland University, Homburg/Saar, Germany.
  • Laschke MW; Institute for Clinical & Experimental Surgery, Saarland University, Homburg/Saar, Germany.
  • Cucchiarini M; Center of Experimental Orthopaedics, Saarland University, Homburg/Saar, Germany.
  • Madry H; Center of Experimental Orthopaedics, Saarland University, Homburg/Saar, Germany.
Am J Sports Med ; 52(5): 1336-1349, 2024 Apr.
Article em En | MEDLINE | ID: mdl-38482805
ABSTRACT

BACKGROUND:

Restoration of osteochondral defects is critical, because osteoarthritis (OA) can arise.

HYPOTHESIS:

Overexpression of insulin-like growth factor 1 (IGF-1) via recombinant adeno-associated viral (rAAV) vectors (rAAV-IGF-1) would improve osteochondral repair and reduce parameters of early perifocal OA in sheep after 6 months in vivo. STUDY

DESIGN:

Controlled laboratory study.

METHODS:

Osteochondral defects were created in the femoral trochlea of adult sheep and treated with rAAV-IGF-1 or rAAV-lacZ (control) (24 defects in 6 knees per group). After 6 months in vivo, osteochondral repair and perifocal OA were assessed by well-established macroscopic, histological, and immunohistochemical scoring systems as well as biochemical and micro-computed tomography evaluations.

RESULTS:

Application of rAAV-IGF-1 led to prolonged (6 months) IGF-1 overexpression without adverse effects, maintaining a significantly superior overall cartilage repair, together with significantly improved defect filling, extracellular matrix staining, cellular morphology, and surface architecture compared with rAAV-lacZ. Expression of type II collagen significantly increased and that of type I collagen significantly decreased. Subchondral bone repair and tidemark formation were significantly improved, and subchondral bone plate thickness and subarticular spongiosa mineral density returned to normal. The OA parameters of perifocal structure, cell cloning, and matrix staining were significantly better preserved upon rAAV-IGF-1 compared with rAAV-lacZ. Novel mechanistic associations between parameters of osteochondral repair and OA were identified.

CONCLUSION:

Local rAAV-mediated IGF-1 overexpression enhanced osteochondral repair and ameliorated parameters of perifocal early OA. CLINICAL RELEVANCE IGF-1 gene therapy may be beneficial in repair of focal osteochondral defects and prevention of perifocal OA.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoartrite / Fator de Crescimento Insulin-Like I / Cartilagem Articular Limite: Animals Idioma: En Revista: Am J Sports Med Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoartrite / Fator de Crescimento Insulin-Like I / Cartilagem Articular Limite: Animals Idioma: En Revista: Am J Sports Med Ano de publicação: 2024 Tipo de documento: Article