Calcium and disease: molecular determinants of calcium crystal deposition diseases.
Calcium and disease: molecular determinants of calcium crystal deposition diseases.
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钙与疾病：钙晶体沉积疾病的分子决定因素。
DOI：
10.1007/pl00000704
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Misra,RP
中科院分区：
文献类型：
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作者：
Misra,RP
碱性磷酸钙（羟基磷灰石、磷酸八钙和磷酸三钙）（BCP）和二水合焦磷酸钙结晶（CPPD）的沉积与多种与衰老相关的病症有关，包括骨关节炎、软骨变性和假痛风。这些钙沉积疾病是钙调节基因表达变化如何直接导致致病后果的一些研究最好的例子。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，就会导致组织损伤。将培养的细胞暴露于晶体会通过钙依赖性机制诱导细胞原癌基因（例如 c-fos、c-mycan 和 c-jun）的表达，并且这种反应可以被潜在的治疗化合物磷酸柠檬酸盐阻断。 c-fos和c-jungenes的激活直接参与金属蛋白酶如胶原酶和溶基质素的表达，表明晶体介导的这些基因的激活直接参与发病机制。在这篇综述中，讨论了晶体介导的细胞激活分子机制的最新进展。
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-mycand c-jun, by a calcium-dependent mechanism, and this response can be blocked by a potential therapeutic compound, phosphocitrate. Activation of the c-fosand c-jungenes 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.