Targeting VEGF-A in cartilage repair and regeneration: state of the art and perspectives.

Osteoarthritis (OA) is the most common joint disorders in western populations, and is characterized by a progressive degradation of articular cartilage (AC) leading to loss of joint function. Methods to cure, delay or prevent the onset of OA and/or improve AC repair strategies have high clinical and socioeconomic impact. Possible innovative strategies envisioned for early OA treatments or cartilage repair include the implantation/injection of mesenchymal progenitors (MPs)-based constructs or cell-free bioactive scaffolds/hydrogel coupled with the controlled recruitment and instruction of resident MPs or AC. However, these tissue engineering-based strategies still suffer from unreliable outcomes with poor fibro-cartilaginous repair and blood vessel invasion. In such conditions Vascular Endothelial Growth Factor (VEGF) family has been shown to play a key role in controlling AC catabolism on one hand and angiogenesis on the other as a crucial step for endochondral ossification of MPs, ultimately leading to progressive breakdown of the neo-formed matrix. This review aims to provide a summary of relevant relationships between impaired angiogenesis, OA and cartilage regeneration highlighting how VEGF might play a paramount role in the pathophysiology of cartilage aging or degeneration as well as in cartilage repair.