Osteoarthritis (OA) as a debilitating affliction of joints currently affects millions of people and remains an unsolved problem. The disease involves multiple cellular and molecular pathways that converge on the progressive destruction of cartilage. Activation of cartilage regenerative potential and specific targeting pathogenic mediators have been the major focus of research efforts aimed at slowing the progression of cartilage degeneration and preserve joint function. This review will summarize recent key discoveries toward better understanding of the complex mechanisms behind OA development and highlight the latest advances in basic and clinical research in the approach for cartilage regeneration. Prospectively, more potent therapeutic strategies against progressive cartilage deterioration may use a combination of cytotherapy, pharmacotherapy, and bioscaffoldings for improved chondrogenic differentiation and stem/progenitor cell homing as well as the concomitant reduced enzymatic matrix degradation and inflammation. Further, treatments need to be provided with increased preciseness of targeted therapy. One might expect that the regenerative therapies could potentially control or even possibly cure OA if performed at early stages of the disease.
