Conditioning and Scaffolding of Chondrocytes: Smart Steps Towards Osteoarthritis Gene Therapy

Abstract

Osteoarthritis (OA), the most common form of arthritis, is a chronic degenerative joint disease that remains a leading cause of chronic disability in the aged population and a financial burden on healthcare resources. It affects approximately 15% of the world’s human population over 60 years of age (Wolf & Pfleger, 2003) and has even higher prevalence in dogs (Johnston, 1997), cats (Godfrey, 2005) and horses (Trumble et al., 2001). It is established that OA in dogs and horses has a model character for the human disease since it parallels the human form of OA in all aspects (Innes & Clegg, 2010). The pathogenesis of OA is characterized by an imbalance in the network of anabolic and catabolic processes through complex interactions of mechanical and biochemical forces (M.B. Goldring, 2001; Sandell & Aigner, 2001). This imbalance leads, inevitably, to progressive articular cartilage destruction, osteophyte formation, subchondral bone remodelling and chronic inflammation (M.B. Goldring & S.R. Goldring, 2007; MartelPelletier & Pelletier, 2007). These events are further manifested by a loss of both tissue architecture and joint functionality, painful limited movement, disability and an inferior quality of life (Abramson & Yazici, 2006; Buckwalter et al., 2006; Pelletier et al., 2001). Despite major progress over the last few years, we still have a lot more to understand about the aetiology, pathogenesis and progression of OA. A complete therapy for OA still remains elusive as manifold efforts made in this direction failed to provide a successful long-term remedy. The therapeutic strategies for OA have been predominantly directed to (i) alleviate symptomatic pain by suppressing the inflammatory process, (ii) reducing the cartilage degenerative process or (iii) enhancing cartilage regeneration. However, none has so far been applied to achieve all the three objectives. Non-pharmacologic and pharmacologic treatments have been employed for early OA while surgical interventions for partial or total joint replacement are often indicated in advanced