Articular cartilage is a remarkable tissue, both in its material properties and cellular function. It is capable of withstanding millions of loading cycles without mechanical failure, all while operating with minimal metabolic demand. Despite its durability, cartilage is susceptible to both age-related degeneration and traumatic injury. Post-traumatic osteoarthritis (PTOA), which results from aberrant joint loading, is one such degenerative condition. This traumatic injury (such as an ACL tear or ankle sprain) causes chondrocyte death, inflammation of multiple joint tissues, and eventual joint dysfunction. Currently, there are no disease-modifying treatments for post-traumatic osteoarthritis. Moreover, the mechanisms underlying the progression of PTOA (i.e. why some joint injuries progress to PTOA while others do not) remain poorly understood. Mitochondria have emerged as key regulators in the response of cartilage to mechanical injury. Beyond their classical role in ATP production, mitochondria modulate several aspects of chondrocyte physiology, including redox balance, calcium signaling, and cell survival. Mechanical injury of cartilage leads to mitochondrial dysfunction, which in turn contributes to chondrocyte apoptosis and the propagation of degenerative signaling cascades. Mitochondrial damage has been implicated in the early stages of PTOA, making these organelles a critical target for both understanding disease mechanisms and developing new therapeutic approaches. The ability of mitochondria to influence inflammation, oxidative stress, and even intercellular communication suggests they may play a central role in determining whether cartilage returns to homeostasis or progresses toward degeneration following injury. This thesis explore PTOA from both an etiological and therapeutic perspective. Chapter one discusses the cellular response of cartilage to mechanical injury, with a focus on the role of mitochondria in chondrocyte mechanotransduction and cartilage degeneration. Chapter two employs an ex vivo model to examine the effects of combined cartilage impact and sliding, revealing a critical time window following injury that may shape disease outcomes. Chapter three utilizes a novel cartilage/mesenchymal stem cell co-culture system to investigate whether mitochondrial transfer can occur through the extracellular matrix of cartilage. Chapter four investigates the differing mechanisms of mitochondrial transfer in traditional 2D culture systems versus 3D explant models.