Osteoarthritis (OA) is the most frequent joint disease in adult. It is responsible for disability and increased mortality. There is no efficient treatment and OA leads to cartilage degradation and joint destruction. Cartilage calcification favors cartilage degradation and worsens OA disease. It is composed of calcium orthophosphate, mainly as carbonated apatite, and calcium pyrophosphate dihydrates (CPPD) crystals. These crystals stimulate the production of catabolic mediators and proteolytic enzymes by joint cells. How these crystals activate cells remains unclear, especially their interactions with cell membrane and intracellular outcomes. Moreover, their individual role in OA is unknown since current imaging techniques possess low capacity to discriminate apatite from CPPD crystals. OASIS project aims: 1/ in fundamental studies to decipher calcium crystal-cell membrane interactions, crystal internalization and intracellular crystal outcomes and ; 2/ in applied issues to optimize spectral multi-energy computerized tomography (SPCCT) acquisition and analysis procedures allowing discrimination between apatite and CPP crystals in OA patients. OASIS project involves a consortium of 5 multidisciplinary academic partners (physicians, chemists, cell biologists, physicists and computer scientists) and an industrial partner (Canon Medical System), well-renowned as CT constructor. This consortium possesses complementary skills including a unique know-how in the synthesis of pure phase apatite, CPPD crystals and fluorescent organic nanoparticles (FON), a mastery of cellular and physico-chemical analysis techniques (Raman spectroscopy, X-ray diffraction, atomic force microscopy (AFM)), deep knowledge of scanner procedures and the access of cohort of well-phenotyped patients and the last spectral CT prototype (AQUILION PRISM). We achieved for the first time to obtain stable FON-coupled calcium phosphate crystals which will allow their internalization and intracellular follow-up. In addition, first tests showed the ability of the spectral CT AQUILION PRISM to differentiate CPPD crystals contained in quadriceps muscle from apatite contained in the femur. These preliminary results guarantee the success of this project. This project will include nanoscale characterization, cellular and animal studies and end with application in patient care. FON-coupled crystals will serve to study their cell membrane interactions and intracellular outcomes using AFM and confocal microscopy in artificial membrane, macrophage and in vivo models. Blocks of apatite or CPPD crystals with different size and mass, grafted in mouse quadriceps and then embedded in resin, will permit ex-vivo identification of SPCCT optimal parameters that discriminate apatite from CPPD crystals. These parameters will be applied in OA patients who will undergo total knee joint replacement surgery. SPCCT results will be compared to ex vivo analysis performed on surgical samples. The capacity to differentiate apatite from CPPD crystals will be a major step in the understanding of OA pathogenesis and allow a better disease management. OASIS project possesses high valorization potential in fundamental and applied issues. Identification of cellular activation mechanisms will open new therapeutic targets and understanding of calcium phosphates crystal internalization mechanisms can be generalized to other inorganic particles. Similarly, the SPCCT diagnosis procedures that permit discrimination between apatite and CPPD crystals can be applied to other calcification tissues and fields including kidney stones, vessel calcification, tumor calcification, etc… These procedures will be integrated in software of future CT.