GAIT-2-OA · Can biomechanical measurements of joints predict severity of osteoarthritis?

Osteoarthritis (OA) is a painful and disabling, multi-factorial disease with strong genetic and environmental determinants. The natural form of OA that arises spontaneously in Str/ort mice has been used as a model for human OA joint degeneration. This model is limited, however, because it is impossible to grade OA incidence and severity non-invasively in mice. Locomotor biomechanics provides a unique tool for non-invasively assessing knee dynamics, and has already been used to detect gait modifications in humans. Such gait analyses are directly transferable to mice. Our pilot data suggest that OA-prone Str/ort mice, in which the joints deteriorate rapidly with ageing, can readily be categorised by temporal changes in gait. Our hypothesis is that deterioration or deviation in individual mouse gait from normal will provide a non-invasive measure of joint degeneration.Our first aim is to examine the heritability of histological osteoarthritis (OA) severity and drop-out age, and their genetic and phenotypic correlations. Our second aim is to assess the relationship between different aspects of gait measurements and OA severity in Str/ort mice, and to assess the predictability of gait measurements on drop-out age. The third aim is to assess the degrees of asymmetry of individuals’ gait measurements (left versus right and front versus rear limbs) during the development of OA in Str/ort mice and compare these to changes in gait during normal healthy ageing in non OA-prone, mice.Identifying new statistically-defined and robust methods of OA detection in the mouse that do not require sacrifice would radically change how OA research might be conducted using this species and accelerate translation of new therapies.""