Vascular mechanisms in osteoarthritis.
Superficial injury and fibrillation of articular cartilage as a consequence of ageing, genetic, hormonal or mechanical factors are not necessarily associated with joint pain. However, failure of joint cartilage accompanied by synovitis and abnormalities in subchondral bone and its vasculature generally is, the syndrome being known as osteoarthritis. We suggest that the progression of early cartilage fibrillation to symptomatic OA arises initially as a consequence of the release into synovial fluid of cartilage-derived antigens that activate joint lining macrophages and circulating leukocytes, thereby establishing a synovitis. Pro-inflammatory mediators and pro-coagulant factors etc. not only perpetuate cartilage destruction but also promote a state of hypercoagulation, hypofibrinolysis, thrombosis and ischaemic bone necrosis at compromised sites such as in the subchondral vasculature. These events are augmented by ageing and associated hormonal changes. On the basis of this hypothesis we suggest that anti-thrombotic/anti-lipidaemic agents that also exhibit anti-inflammatory activity could be effective anti-osteoarthritic drugs. Experimental studies are described which support this proposal.
Ghosh
P
P
Institute of Bone and Joint Research, Department of Surgery, University of Sydney, Level 5, University Clinic, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia.
Cheras
P A
PA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001175:Arthrography; D001778:Blood Coagulation Disorders / Q000097:blood / Q000150:complications* / Q000473:pathology; D002358:Cartilage, Articular / Q000098:blood supply* / Q000187:drug effects; D004195:Disease Models, Animal; D005342:Fibrinolysis; D006801:Humans; D007596:Joints / Q000473:pathology; D010003:Osteoarthritis / Q000097:blood / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D010426:Pentosan Sulfuric Polyester / Q000627:therapeutic use; D013585:Synovitis / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D019851:Thrombophilia
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010426:Pentosan Sulfuric Polyester