This project addresses a critical clinical need for the VA. Knee pain due to progressive joint degeneration and eventual osteoarthritis (OA) are leading causes of disability, particularly in Veterans who are affected by OA at greater frequency and younger ages than the general population. Knee osteoarthritis is a progressive disease for which current treatment is palliative until complete joint destruction occurs and prosthetic knee replacement is performed. Cortisone injections have been widely used for more than 60 years to treat pain and swelling, but have also shown detrimental effects to articular cartilage. This introduces high clinical need for an injection therapy to improve joint pain and function while preserving cartilage health, especially in those with early disease where there is substantial remaining articular cartilage. Recently, intra-articular autologous platelet rich plasma (PRP) injections have gained traction as a promising new treatment for knee OA that can not only provide symptomatic relief but also potentially contribute growth factors to stimulate endogenous joint repair processes. However, the mechanisms of action of PRP are unknown as are the clinical outcomes in Veterans. Our preliminary data also shows substantial variability between individuals in the biological composition of autologous PRP. In this era of personalized and precision medicine, we propose to examine the outcomes of PRP treatment, and whether individual differences in PRP composition correlate with objective metrics of changes to ambulatory function and cartilage matrix structure following PRP injection treatment for early knee OA in Veterans. Achieving the Aims of this proposal will determine whether intra-articular injection of autologous platelet enriched plasma to treat early knee OA in Veterans and additional women, given within the actual clinical setting, results in positive treatment effects. The information gained will also fill critical knowledge gaps by elucidating potential mechanisms of action for PRP injections in the treatment of symptomatic early knee OA and combining objective scientific assessment (gait analysis and MRI) with standard patient-reported outcomes (PRO). Finally, the new knowledge gained will improve clinical care by informing on factors important to optimal patient selection for this new treatment.