1. ¹Laboratory for Experimental Orthopaedics, Department of Orthopaedics and Orthopaedic Surgery, Saarland University Medical Center, Homburg, Germany
2. ²Division of Experimental Medicine, Harvard Institutes of Medicine and Beth Israel Deaconess Medical Center, Boston, MA, USA
3. ³Department of Biostatistics and Medicine, Children's Hospital, Harvard Medical School, Boston, MA, USA
4. ⁴Institute for Clinical and Experimental Surgery, Saarland University Medical Center, Homburg, Germany
5. ⁵Department of Orthopaedic Surgery, Indiana University, Indianapolis, IN, USA

Correspondence: Magali Cucchiarini, Laboratory for Experimental Orthopaedics, Department of Orthopaedics and Orthopaedic Surgery, Saarland University Medical Center, D-66421 Homburg, Germany. Fax: +49 6841 16 24988. E-mail: mmcucchiarini@hotmail.com

Received 9 August 2004; Accepted 1 March 2005.

Abstract

Therapeutic gene transfer into articular cartilage is a potential means to stimulate reparative activities in tissue lesions. We previously demonstrated that direct application of recombinant adeno-associated virus (rAAV) vectors to articular chondrocytes in their native matrix in situ as well as sites of tissue damage allowed for efficient and sustained reporter gene expression. Here we test the hypothesis that rAAV-mediated overexpression of fibroblast growth factor 2 (FGF-2), one candidate for enhancing the repair of cartilage lesions, would lead to the production of a biologically active factor that would facilitate the healing of articular cartilage defects. In vitro, FGF-2 production from an rAAV-delivered transgene was sufficient to stimulate chondrocyte proliferation over a prolonged period of time. In vivo, application of the therapeutic vector significantly improved the overall repair, filling, architecture, and cell morphology of osteochondral defects in rabbit knee joints. Differences in matrix synthesis were also observed, although not to the point of statistical significance. This process may further benefit from cosupplementation with other factors. These results provide a basis for rAAV application to sites of articular cartilage damage to deliver agents that promote tissue repair.