Osteoarthritis (OA) is associated with muscle strength decline, cartilage breakdown and pain-related disability. The annual estimated out-of-pocket cost per patient for the management of knee OA alone is estimated to be $2600 with total annual expenses estimated to be $5700. The proposed investigation will be the first to rigorously evaluate the influence of two modes of resistance exercise (RX) on knee OA pain and functional impairment. Use of RX may help with resolution of OA symptoms, decrease medical management costs and delay or avoid costly knee replacements. It is unknown whether there is differential efficacy of two modes of resistance exercise on knee pain, cartilage turnover and physical function: eccentrically-focused exercise (ERX) and traditional concentrically-focused exercise (CRX). Using innovative prototype resistance exercise equipment, we will conduct a four-month, randomized, single-blind controlled study of the relative efficacy of ERX and CRX compared to a non-exercise control (CON) condition on knee pain, physical function and cartilage turnover in older adults with knee OA (aged 60-85). Primary Aim of this study is to determine if ERX will reduce knee pain in older adults (using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC Score) more than CRX or CON. Secondary Aim 1 will be to determine if ERX improves physical function and habitual physical activity more than CRX and CON by month four (assessed by a functional test battery). Secondary Aim 2 will test whether ERX will induce greater changes in cartilage biomarker turnover than CRX or CON by month four (using C-propeptide of type II procollagen [CTX-II], Collagen Type II C- telopeptide [CPII]). This proposed study is a prospective, randomized, controlled study (RCT) that will determine whether one of two resistance exercise protocols improves pain, physical function, and cartilage metabolism in older persons with knee OA. This is a repeated-measures, three group design. Participants (n=90) will be randomly assigned to one of three study groups (n=30 per group). The three groups will include a non-exercise control (CON) group, a concentrically focused resistance training group (CRX; one set/ exercise, two sessions/ week) and an eccentrically focused resistance training group (ERX; one set/ exercise, two sessions/ week). Study measures will be collected at baseline and at month four. Men and women with OA related knee pain will be eligible for this study. Demographics, body composition, OA history and severity will be collected as descriptive variables. Mobility and physical function tests (Six minute walk test, 7-day pedometer test, chair rise time and stair climb time), knee pain (WOMAC Score), and biomarkers of cartilage turnover (CTX-II, CPII) will be performed at baseline and after four months of resistance exercise or control period. The uniqueness of the proposed study exists on two fronts: the comparative efficacy of two muscle contraction types on knee OA symptoms and function in older adults will be determined, and the effects of two forms of resistance exercise on the levels of biomarkers of cartilage turnover will be assessed. The candidate is an Assistant Professor in the Department of Orthopaedics and Rehabilitation at the University of Florida. He has a PhD in Exercise Physiology from the University of Florida and is board certified in Physical Medicine and Rehabilitation. The candidate is also a Junior Scholar in the Claude D. Pepper Older Americans Independence Center (OAIC). His research focus is to examine the influence of resistance exercise on physical function and physiological adaptations in clinical populations, particularly older adults. To achieve the goal of becoming an independent clinician scientist, the candidate has established the following objectives for this award: 1) Enhance his clinical research skills; 2) Advance his current knowledge of the pathogenesis and pathophysiology of osteoarthritis with a primary focus on the biochemical and biomechanical changes in the knee joint and articular cartilage ; 3) Acquire background knowledge and technical skills relevant to the development of knee OA including both biomechanical and biochemical analysis; 4)Improve grant writing proficiency. The candidate has developed a mentoring and collaborative team composed of accomplished senior faculty. The primary mentor is Dr. Christiaan Leeuwenburgh, from the Department of Aging and Geriatrics. The Co-mentors are Drs. Scott banks and Steven Ghvizzani. Dr. Vincent's mentors have extensive experience with osteoarthritis research and mentoring junior faculty. With their assistance a three-year career development plan has been designed to take advantage of select didactic courses, mentored laboratory experiences, conference/workshop attendance, structured meetings and regularly scheduled seminars. Dr. Vincent will also have guidance from Dr. John Shuster to assist with his statistical analysis skill development and from Dr. Joanne Jordan from the University of North Carolina who will help with clinical correlation to OA and research design. In addition to a distinguished and experienced mentoring team, Dr. Vincent will have full access to the necessary facilities and support offices to conduct the proposed study. The primary location for data collection for the proposed study will be the Human Dynamics Laboratory within the Orthopaedics and Sports Medicine Institute at The University of Florida (UF). This study will also utilize the research cores (Recruitment, Clinical Research, Biostatistic and Data Management, and Genomics and Biomarkers) of the OAIC within the UF Institute on Aging, and the resources of the Clinical and translational Science Institute. PUBLIC HEALTH RELEVANCE: Osteoarthritis elicits quadriceps muscle deficits and cartilage breakdown, both of which contribute to pain and functional impairment in the older adult. A possible method to combat these disease processes is resistance exercise training. This project will examine whether there are differential improvements in osteoarthritis symptoms, impairment and cartilage turnover using a novel eccentric resistance exercise program compared with concentric focused resistance exercise in older persons.