Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy Martin Stolz M.E. Müller Institute for Structural Biology, Biozentrum,University of Basel, Switzerland. Despite the high prevalence of osteoarthritis (OA) in people over 50, currently there exist no treatments that arrest or reverse the degeneration of the articular cartilage (AC). Pathological changes of AC are initiated at the molecular (nanometer) scale, from where they spread to higher levels of cartilage’s hierarchical architecture and cause progressively irreversible structural and functional damage. Hence, early detection and monitoring progression of OA in patients is a prerequisite for developing more effective prophylactic therapies and drugs aimed at halting the disease. Towards this goal, first we document the sensitivity of nano scale IT AFM to follow age-related surface topographical and biomechanical changes occurring in hip AC of wild type mice. Next, we provide evidence that IT AFM is capable to detect early pathological alterations of the AC in the OA model collagen IX-deficient mice. Finally, we investigated AC samples from patients undergoing joint arthroplasty. Our results demonstrate that changes of aging and osteoarthritic AC surfaces are detectable at the nanometer scale. Therefore, we suggest to develop novel, IT AFM-based nanotools to eventually detect the early onset of OA in situ by a minimally invasive arthroscopic intervention.