Calcium crystal effects on the cells of the joint: implications for pathogenesis of disease.
In the past three years, there has been considerable progress in delineating the mechanism of calcium-containing crystal-induced cell activation: (1) the identification of Ca2+ influx and p42/44 mitogen-activated protein kinase activation as the signal transduction pathways; (2) induction of nuclear transcription factors of cyclic adenosine monophosphate (cAMP) response element binding protein, activator protein-1, and nuclear factor kappaB; (3) the differential role of crystal endocytosis and dissolution in crystal-induced metalloproteinase synthesis and mitogenesis; (4) crystal upregulation of matrix metalloproteinases, including MMP-13 but downregulation of tissue inhibitor of metalloproteinase-1 and -2, thus magnifying the degenerative effect of crystals. Phosphocitrate, a specific inhibitor of biologic effect of calcium crystals, reverses the degenerative effects of crystals.
Cheung
H S
HS
Geriatric Research Education and Clinical Center, Miami Veterans Affairs Medical Center and Division of Rheumatology and Immunology, University of Miami School of Medicine, FL, USA. hcheung@med.miami.edu
D002130:Calcium Phosphates / Q000378:metabolism*; D002131:Calcium Pyrophosphate / Q000378:metabolism*; D002805:Chondrocalcinosis / Q000209:etiology* / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D003460:Crystallization; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D006801:Humans; D007596:Joints / Q000378:metabolism* / Q000473:pathology; D053509:Matrix Metalloproteinase 13; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis; D015854:Up-Regulation
D002130:Calcium Phosphates; D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C485829:calcium phosphate, dibasic, anhydrous; D002131:Calcium Pyrophosphate