Screen of FDA-approved drug library identifies vitamin K as anti-ferroptotic drug for osteoarthritis therapy through Gas6

Shi Y, Li S, Zhang S, et al. · Journal of Pharmaceutical Analysis

Vitamin K1 was the strongest anti-ferroptotic hit in a screen of 1,527 FDA-approved compounds in chondrocytes, blocked matrix degradation, and roughly halved cartilage-damage scores when injected into mouse knees. Menaquinone-4 and menadione rescued chondrocytes too, so the effect is not particular to K1 in cells. Knocking down Gas6, itself a vitamin-K-dependent protein, abolished the protection, which is what ties it to Gas6 and the AXL/PI3K/AKT axis.

Population

High-throughput screen in chondrocytes plus a destabilisation-of-the-medial-meniscus mouse osteoarthritis model

Intervention

Vitamin K, delivered by intra-articular injection in vivo

Comparator

Untreated osteoarthritic mice and cells

Limitations

Intra-articular injection in mice, which says nothing about what a swallowed capsule reaches; a screening hit followed up in one laboratory; the form injected was K1, and the long-chain MK-7 sold as a supplement was not among the three tested. In the mice, vitamin K did not raise Gas6 expression — the Gas6 dependence rests on the knockdown arm.