Mechanical trauma through repetitive, high-impact sport contributes to the onset of osteoarthritis. Mechanical trauma disrupts cell cytoskeletal organization (Blain, 2009), which is important in maintaining cell integrity. Since tamoxifen has been shown to have anti-calmodulin effects (Hall et al. 1999), acting upstream of actin regulatory proteins, this study was designed to investigate whether this compound exerts a chondro-protective effect following mechanical trauma. Cartilage explants were dissected from the joints of 18-21 month old steers (obtained from a local abattoir) into DMEM. Explants were incubated for 1h in either: isotonic (280mOsm), hypertonic (380 mOsm) or tamoxifen (10μM) supplemented DMEM and subsequently subjected to a single impact as previously described (Bush et al., 2005). Chondrocyte viability, volume and relative F-actin concentration were determined by confocal microscopy and data expressed as mean ± s.e.m; (Student’s t-test: p<0.05), n=45 cells each from 3 distinct experiments. Explants in isotonic DMEM exhibited a decrease in cell viability from 85±0.05% to 45±2.52% at 48h post impact; p<0.05. Conversely, when incubated with hypertonic DMEM or 10μM tamoxifen there was no significant decrease in chondrocyte viability from 90±3.65% and 95±4.51% to 90±2.63% and 88±3.34% respectively at 48h. Tamoxifen incubated samples displayed a decrease in cell volume (p<0.01) from 716±23μm3 to 424±16μm3 at time 0, when compared to control conditions. However explants incubated in isotonic and hypertonic DMEM all exhibited an impact-induced decrease in cell volume 48hrs post impact, from 716±23μm3 and 578±31μm3 to 516±15μm3 and 302±12μm3 (p<0.05) respectively, whereas tamoxifen incubated explants displayed no significant decrease in cell volume post-impact, from 424±16μm3 to 432±5μm3. Additionally pre-incubation with tamoxifen resulted in an decrease (p<0.05) in F-actin:volume (0.75±0.04AU) when relative to non-treated samples prior to mechanical trauma, conversely hypertonic pre-incubation displayed an increase (p<0.05) in F-actin:volume (1.21±0.06AU). Interestingly, explants pre-treated with isotonic and hypertonic DMEM all exhibited an impact-induced decrease (p<0.01) in F-actin:volume to 0.58±0.03AU and 0.73±0.04AU respectively at 48hrs post impact, relative to non-treated samples prior to mechanical trauma. Conversely tamoxifen treated explants showed no significant change in F-actin:volume at 48hrs (0.73±0.04AU). These data suggest that tamoxifen exhibits a chondro-protective effect in an in vitro model of mechanical trauma by inhibiting impact-induced cell volume and F-actin decrease.