Anthraquinone-2,6-disulfonic acid as a disease-modifying osteoarthritis drug: an in vitro and in vivo study.

Pharmacologic treatment of osteoarthritis has been confined mostly to analgesic or nonsteroidal antiinflammatory drugs that only modify the symptoms. We asked whether anthraquinone-2,6-disulfonic acid might act as a disease-modifying osteoarthritis drug. We evaluated the in vitro inhibitory effect of anthraquinone-2,6-disulfonic acid on cathepsin B activity and proteoglycan release from cultured rabbit cartilage challenged with interleukin-1beta in comparison with diacerhein, the prodrug of rhein. We studied the in vivo activity in an experimental osteoarthritis model induced by medial monolateral meniscectomy in rabbits. After 3 months of treatment with oral anthraquinone-2,6-disulfonic acid or diacerhein at 25 mg/kg/day, the animals were sacrificed and the knees were retrieved; cluster chondrocytes, fibrillations, fissures, and osteophytes were studied on cartilage biopsies. The evidence for disease-modifying activity of anthraquinone-2,6-disulfonic acid was (1) the in vitro dose-dependent inhibition of cathepsin B activity, (2) the in vitro time- and dose-dependent inhibition of interleukin-1beta-stimulated proteoglycan release from the cartilage matrix, and (3) the in vivo reduction of all cartilage degeneration parameters. Our data suggest anthraquinone-2,6-disulfonic acid is worth exploring for treating osteoarthritis.