Osteoarthritis characterizes the joint disease that results in cartilage damage accompanied by bone lesions and synovial inflammation. Joint integrity results from physiological interactions between all these tissues. Local factors such as cytokines and growth factors regulate cartilage remodeling and metabolism as well as chondrocyte differentiation and survival. Tremendous progress has been made through the use of animal models and provided insight for the mechanism of cartilage loss and chondrocyte functions. Surgical, chemical or genetic models have been developed to investigate the role of molecules in the pathogenesis or treatment of osteoarthritis. Indeed, the animal models are helpful to investigate the cartilage changes in relation to changes in bone remodeling. Increased bone resorption occurs at early stage of the development of osteoarthritis, the inhibition of which prevents cartilage damage, confirming the role of bone factors in the crosstalk between both tissues. Among these numerous molecules, some participate in the imbalance in cartilage homeostasis and in the pathophysiology of osteoarthritis. These local factors are potential candidates for new drug targets.