caa a22 4500 475845854 CHVBK 20180406123913.0 cr unu---uuuuu 170329e20000301xx s 000 0 eng 10.1007/PL00000704 doi (NATIONALLICENCE)springer-10.1007/PL00000704 Misra R. P. Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee (Wisconsin 53226, USA), Fax +1 414 456 6510, e-mail: rmisra@mcw.edu, US aut Calcium and disease: molecular determinants of calcium crystal deposition diseases [Elektronische Daten] [R. P. Misra] Abstract.: Deposition of basic calcium phosphate (hydroxyapatite, octacalcium phosphate and tricalcium phosphate) (BCP) and crystalline calcium pyrophosphate dihydrate (CPPD) is associated with a variety of aging-related pathologies, including osteoarthritis, cartilage degeneration and pseudogout. These diseases of calcium deposition serve as some of the best-studied examples of how calcium-regulated changes in gene expression can directly lead to pathogenic consequences. Tissue damage can result when crystals stimulate cells to release matrix-degrading molecules or secrete cytokines that stimulate the release of matrix-degrading molecules. Exposure of cultured cells to crystals induces expression of cellular proto-oncogenes such as c-fos, c-myc and c-jun, by a calcium-dependent mechanism, and this response can be blocked by a potential therapeutic compound, phosphocitrate. Activation of the c-fos and c-jun genes is directly involved in expression of metalloproteinases such as collagenase and stromelysin, suggesting that crystal-mediated activation of these genes is directly involved in pathogenesis. In this review recent advances in the molecular mechanisms responsible for crystal-mediated cell activation are discussed. Birkhäuser Verlag Basel,, 2000 Key words. BCP nationallicence CPPD nationallicence calcium deposition disease nationallicence signal transduction nationallicence gene expression nationallicence https://doi.org/10.1007/PL00000704 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/PL00000704 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Misra R. P. Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee (Wisconsin 53226, USA), Fax +1 414 456 6510, e-mail: rmisra@mcw.edu, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer