Wang KD, Ding X, Jiang N, et al. - As there is a close correlation between dysregulated chondrocyte metabolism and the pathogenesis of osteoarthritis (OA), an extensive exploration of has been done on suppressing chondrocyte catabolism to restore cartilage homeostasis but efforts have been far less invested toward enhancing chondrocyte anabolism. For repurposing clinically approved drugs as potential stimulators of chondrocyte anabolism in treating OA, this study was attempted.

• A Food and Drug Administration-approved drug library was screened; the chondroprotective effects of digoxin were examined in vitro using assays; the therapeutic effects of digoxin were defined using a surgically-induced OA model with the help of assays.

• Using the Health Improvement Network, a propensity-score matched cohort study was done to determine the correlation between digoxin use and the risk of joint OA-associated replacement among patients with atrial fibrillation

• Ouabain and digoxin were identified as stimulators of chondrocyte differentiation and anabolism by performing serial screenings.

• Protection against OA and relief from OA-associated pain were attained using ouabain and digoxin.

• In the cohort study of 56,794 patients, digoxin use was noted to be linked with decreased risk of OA-associated joint replacement.

• Isolation of LRP4 was done as a novel target of digoxin, and deletion of LRP4 was linked with abolition of digoxin’s regulations of chondrocytes.

• Overall, in addition to providing new information concerning digoxin’s chondroprotective action and underlying mechanisms, this study presents new evidence for repurposing digoxin for OA.