Specific inhibition of basic calcium phosphate and calcium pyrophosphate crystal-induction of metalloproteinase synthesis by phosphocitrate.
Specific inhibition of basic calcium phosphate and calcium pyrophosphate crystal-induction of metalloproteinase synthesis by phosphocitrate.
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磷酸柠檬酸特异性抑制碱式磷酸钙和焦磷酸钙晶体诱导的金属蛋白酶合成。
DOI：
10.1016/0925-4439(95)00106-9
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Struve,JA
中科院分区：
文献类型：
--
作者：
Cheung,HS;Sallis,JD;Struve,JA
二水焦磷酸钙（CPPD）和碱性磷酸钙（BCP）晶体沉积病是一组异质性关节炎，是老年人发病的重要原因。这两种晶体诱导成纤维细胞和软骨细胞的有丝分裂和金属蛋白酶（MP）的合成和分泌，这可能会促进关节内组织的降解。我们以前已经表明，磷酸柠檬酸盐（PC），羟基磷灰石结晶的抑制剂，特别是块BCP晶体诱导的有丝分裂在3 T3细胞。这使我们检查PC对BCP和CPPD晶体诱导人成纤维细胞中MP合成的影响。PC（10− 3至10− 4 M）特异性抑制晶体诱导的胶原酶和基质溶解素mRNA的积累，而对表皮生长因子诱导的或基础水平的两种酶的mRNA没有影响。条件培养基的蛋白质印迹（胶原酶）证实PC也阻断了晶体诱导的蛋白酶分泌。由于FOS和JUN蛋白是胶原酶和基质溶解素基因表达的反式激活因子（AP-1），PC（10 - 3 M）可能通过抑制c-fos和c-jun的转录来阻断这两种酶的合成。
Calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP) crystal deposition diseases are a group of heterogeneous arthritides which are a significant source of morbidity in the elderly. Both crystals induced mitogenesis and metalloproteinase (MP) synthesis and secretion by fibroblasts and chondrocytes which may promote degradation of intra-articular tissue. We have previously shown that phosphocitrate (PC), an inhibitor of hydroxyapatite crystallization, specifically blocks BCP crystal-induced mitogenesis in 3T3 cells. This led us to examine the effect of PC on BCP and CPPD crystal induction of MP synthesis in human fibroblasts. PC (10−3to 10−4M) specifically inhibited the crystal-induced collagenase and stromelysin mRNA accumulation while having no effect on epidermal growth factor-induced or basal levels of mRNA for both enzymes. Western blots (collagenase) of conditioned media confirmed that PC blocked crystal-induced proteinase secretion as well. Moreover, PC (10−3M) also blocked the crystal induction of c-fos and c-jun. Sincee FOS and JUN proteins form a transacting activator (AP-1) for expression of collagenase and stromelysin genes, PC may block the synthesis of both enzymes by inhibiting the transcription of c-fos and c-jun.