Basic calcium phosphate crystals as a unique therapeutic target in osteoarthritis.
Osteoarthritis (OA) is the most common form of arthritis that occurs in humans. Despite its prevalence, the pathogenesis of OA is not fully understood. Intraarticular basic calcium phosphate (BCP) (an inclusive term for partially carbonate-substituted hydroxyapatite, octacalcium phosphate and tricalcium phosphate) crystals are implicated in OA and are associated with severe degenerative arthritis characterized by marked synovial hyperplasia, aggravated joint degeneration and large joint effusions. Their pathogenicity relates, at least in part, to their ability to stimulate cellular mitogenesis in a number of cell types including macrophages, porcine articular chondrocytes (PAC) and human fibroblasts (HF) and induce prostaglandin, cytokine and matrix metalloproteinase synthesis and secretion in HF and PAC. Identification of BCP crystals in OA joints remains problematic because of the lack of a simple and reliable analytic procedure. There is currently no drug available that prevents the formation or modifies the biological effects of BCP crystals. This review highlights the recent advances in our knowledge of BCP crystal deposition diseases and discusses the potential therapeutic strategies for BCP crystal-associated OA.
Whelan
Linda C
LC
Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin.
Morgan
Maria P
MP
McCarthy
Geraldine M
GM
D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry*; D019902:Chondrocytes / Q000378:metabolism; D003460:Crystallization; D017886:Durapatite / Q000737:chemistry; D005347:Fibroblasts / Q000378:metabolism; D005944:Glucosamine / Q000737:chemistry; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism* / Q000628:therapy; D011453:Prostaglandins / Q000378:metabolism; D013552:Swine; D014233:Tricarboxylic Acids / Q000737:chemistry
D002130:Calcium Phosphates; D011453:Prostaglandins; D014233:Tricarboxylic Acids; C039013:N-sulfo-2-aminotricarballylate; D017886:Durapatite; C020243:calcium phosphate; D020782:Matrix Metalloproteinases; D005944:Glucosamine