**7. Additional Emerging Targets for the Treatment of Osteoarthritis Using CRISPR**/**Cas9**

While a significant focus is placed on cartilage and the chondrocytes that maintain articular cartilage, there is wide agreement that OA is not simply a disease of the cartilage, but rather of the entire joint, and all of the specific tissue types within the joint play essential roles. Osteocalcin, a small protein hormone secreted by the osteoblasts of the bone, has been studied recently for its endocrine functions, which impact several physiological processes. Lambert and colleagues found in their 2016 study that by applying CRISPR/Cas9 technologies to osteocalcin expression, they were able to improve bone biomechanics and increase the trabecular bone in a rat model system [107].

Additional potential targets for therapy have been identified using CRISPR/Cas9 technology. For example, CRISPR/Cas9 knockout of hyaluronan synthase 2 (HAS2) in rat chondrocytes demonstrated the importance of the glycosaminoglycan hyaluronan, for the retention of aggrecan, a proteoglycan necessary for the functional integrity of the articular cartilage [109]. CRISPR/Cas9 can, therefore, provide fundamental information about the molecular mechanisms required for healthy joint tissue in addition to potential use as a direct treatment.
