Osteoarthritis (OA), with a high prevalence and economic impact, is a progressive diarthrodial joint disease that substantially reduces quality of life and is mainly characterized by degradation of the extracellular matrix (ECM) and the loss of a chondrogenic phenotype in articular cartilage. Strategic targeting of therapeutic genes to OA cartilage may offer potent alternatives for restoring the structure of the damaged cartilage. α2-macroglobulin (α2M), a member of the α2M family of proteins, prevents the degradation of the ECM by inhibiting the activity of a disintegrin-metalloproteinases with thrombospondin motifs (ADAMTSs) and matrix metalloproteinases (MMPs). Sox9, a key chondrogenic transcription factor, plays a crucial role in the development and maintenance of the chondrogenic phenotype. Therefore, modulation of the OA cartilage by genetically modifying the levels of α2M and Sox9 expression may be advantageous in ameliorating the course of OA. To acquire long-lasting expression of the α2M and Sox9 genes, gene transfer systems are required. The chitosan vector system is expected to be useful for direct gene therapy for joint disease. Thus, we conclude that co-expression of the α2M and Sox9 genes, combined with chitosan‑mediated gene delivery, will offer potential as a novel means by which to treat OA via intra-articular injection.

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