title: Anthraquinone-2,6-disulfonic acid as a disease-modifying osteoarthritis drug: an in vitro and in vivo study.
abstract: 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.
authors.affiliation: Laboratory for Pathophysiology of Orthopaedic Implants, Istituti Ortopedici Rizzoli, Bologna, Italy. lucia.savarino@ior.it
authors.forename: Lucia
authors.initials: L
authors.lastname: Savarino
authors.forename: Antonella
authors.initials: A
authors.lastname: Fioravanti
authors.forename: Graziana
authors.initials: G
authors.lastname: Leo
authors.forename: Ruggero
authors.initials: R
authors.lastname: Aloisi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Mian
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology / Q000627:therapeutic use*; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000378:metabolism; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D010003:Osteoarthritis / Q000188:drug therapy*; D011817:Rabbits