**6. Epigenetics as a future therapy for cartilage regeneration**

Articular cartilage has a relatively high incidence of damage due to several factors such as injury, trauma and inflammation. The inflammatory markers could induce a number of MMPs, which could degrade the ECM, as the cartilage has a limited ability to repair and regenerate, resulting in a total loss of cartilage tissue. The destruction and loss of articular cartilage is also central to the development of OA. The research work over the past few decades confirms that epigenetics plays a pivotal role in the phenotypic modulation that articular chondrocytes undergo during OA. Epigenetics changes the normal chondrocytes to 'altered' chondrocytes that overexpress the cartilage-degrading proteins or enzymes such as collagenases and aggregenase and inflammatory mediators. This disruption in homeostatic balance between the matrix production and ECM destruction results in the progression of OA. There is a direct pathological loop that involves inflammation and epigenetic modifications, which accelerates disease progression. Until now, no detailed global methylation analysis has been performed in the pathogenesis of OA. Low penetrance polymorphism in the population partly due to epigenetic modification is the reason for limited data generation to aid in the identification of genes responsible for the genetic susceptibility to OA. A number of inflammatory genes have been identified which are controlled through epigenetics and are directly involved in the pathogenesis of OA (**Table 1**).
