Misra R P
Department of Biochemistry, Medical College of Wisconsin, Milwaukee 53226, USA.
Cell Mol Life Sci. 2000 Mar;57(3):421-8. doi: 10.1007/PL00000704.
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.
碱性磷酸钙（羟基磷灰石、八钙磷酸钙和磷酸三钙）（BCP）以及二水焦磷酸钙晶体（CPPD）的沉积与多种衰老相关病症有关，包括骨关节炎、软骨退变和假性痛风。这些钙沉积疾病是研究得较为透彻的例子，展示了钙调节的基因表达变化如何直接导致致病后果。当晶体刺激细胞释放基质降解分子或分泌刺激基质降解分子释放的细胞因子时，就会造成组织损伤。将培养的细胞暴露于晶体中会通过钙依赖机制诱导细胞原癌基因如c-fos、c-myc和c-jun的表达，而这种反应可被一种潜在的治疗化合物磷柠檬酸盐阻断。c-fos和c-jun基因的激活直接参与诸如胶原酶和基质溶解素等金属蛋白酶的表达，这表明这些基因的晶体介导激活直接参与发病机制。在这篇综述中，我们讨论了负责晶体介导细胞激活的分子机制的最新进展。
