Mechanisms of connective tissue damage by crystals containing calcium.
From available clinical, radiographic, and synovial fluid findings, coupled with in vivo radiolabelled crystal turnover data and in vitro experimental data, a hypothesis has been formulated relative to the pathogenesis of BCP crystal deposition diseases (Fig. 2). Synovial lining cells phagocytose BCP crystals and particulate collagens in the joint fluid. During and/or after internalization these cells are stimulated in a variety of ways: 1) protease synthesis and secretion is relentlessly stimulated, which may damage joint tissues producing clinically evident loss of collagenous tissues including cartilage, bone, and tendon, and which may release additional amounts of crystals and particulate collagens into the synovial fluid, completing a vicious cycle; 2) PGE2 production is greatly augmented; 3) DNA synthesis is stimulated as a result of increased inositol phospholipid turnover and intracellular crystal dissolution. The increased number of synovial cells also augments the total local generation of proteases and prostenoids. Mechanical factors such as trauma or joint overuse also contribute to the pathogenesis of joint destruction as discussed in the article on the clinical aspects of BCP crystal deposition.
D000818:Animals; D002114:Calcinosis / Q000209:etiology; D002130:Calcium Phosphates / Q000378:metabolism / Q000502:physiology*; D002630:Chemotactic Factors / Q000502:physiology; D003240:Connective Tissue Diseases / Q000209:etiology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007592:Joint Diseases / Q000209:etiology*; D008934:Mitogens; D010447:Peptide Hydrolases / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D013582:Synovial Fluid / Q000378:metabolism
D002130:Calcium Phosphates; D002630:Chemotactic Factors; D008934:Mitogens; D011453:Prostaglandins; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; D010447:Peptide Hydrolases; C485829:calcium phosphate, dibasic, anhydrous