Stimulation of synovial fibroblasts by calcium oxalate and monosodium urate monohydrate. A mechanism of connective tissue degradation in oxalosis and gout.
The responses of cultured rabbit synovial fibroblasts to amorphous and microcrystalline calcium oxalate were compared with responses to MSUM. Like urate crystals, crystalline calcium oxalate (but not amorphous oxalate) caused marked stimulation of secretion of latent collagenase and PGE2 after 3 days of culture without significant change in cell protein or gross cellular morphology. Collagenase rose from undetectable levels in control cultures to 32.4 +/- 6.0 and 27.4 +/- 7.9 U/mg of cell protein for crystalline calcium oxalate and MSUM, respectively. PGE2 rose from a control level of 0.24 +/- 0.14 to 19.47 +/- 5.15 and 23 +/- 4.84 micrograms/mg of cell protein for crystalline calcium oxalate and sodium urate compared to 1.22 +/- 0.48 microgram for amorphous calcium oxalate. Although the crystalline species studied caused LDH in the media to increase threefold, this was minimal. Cell stimulation by amorphous oxalate and the crystals did not correlate with membranolytic potential as measured with an erythrocyte lysis assay. Stimulation of resident synovial cells by crystalline calcium oxalate and sodium urate may contribute to the chronic inflammation and destruction of joint tissues that occurs in oxalosis and gout.
D000818:Animals; D002129:Calcium Oxalate / Q000494:pharmacology* / Q000652:urine; D003240:Connective Tissue Diseases / Q000503:physiopathology*; D003460:Crystallization; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects*; D006073:Gout / Q000503:physiopathology*; D006461:Hemolysis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D003012:Microbial Collagenase / Q000378:metabolism; D011458:Prostaglandins E / Q000096:biosynthesis; D011817:Rabbits; D013582:Synovial Fluid / Q000166:cytology*; D014527:Uric Acid / Q000494:pharmacology*
D011458:Prostaglandins E; D002129:Calcium Oxalate; D014527:Uric Acid; D007770:L-Lactate Dehydrogenase; D003012:Microbial Collagenase; D015232:Dinoprostone