The resulting downstream effect is a disorganized type II collagen network most likely due to the absence of type IX collagen which is needed to crosslink type II collagen. Altogether, the loss of these proteins from the Myricetrin matrix and the poorly organized ECM structure of the articular cartilage contribute to joint abnormalities and early onset osteoarthritis characteristic of both PSACH and MED/EDM1. In contrast, COMP knock-out mice are normal in all growth parameters with only mild growth plate disturbances and flattening of the articular cartilage surface only found with exercise. This suggests that the presence of mutant COMP has a greater negative impact on skeletal growth and development than the absence of normal COMP. Moreover, these findings also suggest that surpressing intracellular retention of mutant COMP by reducing COMP expression could be used as a therapeutic approach. RNA interference technology is one method to selectively reduce expression of a particular gene. The challenges to using RNAi therapy in a clinical setting are significant and this barrier is particularly difficult with avascular tissues such as cartilage. Preventing or reducing PSACH cellular pathology will require long-term reduction of COMP expression because chondrocytes produce COMP throughout life. However, there is active research to develop technologies capable of delivering therapeutics including shRNA delivery vectors to cartilage tissue. One system relies upon cell-specific antibodies to attach to viral envelope proteins for specific delivery or nanoparticles to deliver plasmids or siRNAs. Similarly, polypeptide ligands that bind to cartilage are designed for delivery into this difficult tissue. Additionally, topical administration of siRNAs have been shown to deliver sufficient levels of Liquidambaric-lactone antisense RNAs to reduce the target mRNA in mice joints. Osteopontin siRNA cream prevents severe and irreversible damage to bone and cartilage caused by collagen antibodyinduced rheumatoid arthritis in a mouse model. This topical delivery method has not been verified in larger animals where thicker tissue may inhibit sufficient penetration.