Rosenthal A K, Cheung H S, Ryan L M
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
Arch Biochem Biophys. 1989 Aug 1;272(2):386-92. doi: 10.1016/0003-9861(89)90232-4.
The disordered production of inorganic pyrophosphate (PPi) by articular cartilage is thought to have an important role in the pathogenesis of calcium pyrophosphate dihydrate deposition disease and perhaps osteoarthritis. We have previously shown that fetal calf serum added to the culture media of porcine articular cartilage explants increases the elaboration of PPi into the ambient media. We have examined this PPi stimulatory activity by studying the effects of adult human serum (HS), serum derived from adult human plasma (HP), and an acid-alcohol extract of human platelets (PE) on PPi production in cartilage organ culture. Ten percent HS produces a 1.4-fold increase in PPi production after 48 h of culture, while cartilage incubated in media containing 10% HP produces no more PPi than that incubated in media alone. PE stimulates a mean 2-fold increase in PPi production at 48 h in the presence of low concentrations of HP, and has no effect alone. It does not appear to up-regulate the activity of the ectoenzyme nucleoside triphosphate pyrophosphohydrolase (NTPPPH), nor does it promote the release of enzyme substrate into the extracellular space. Cartilage exposed to 0.5% HP and PE has 1.51 +/- 0.36 units of NTPPPH activity whereas cartilage exposed to 0.5% HP alone has 1.52 +/- 0.41 units of enzyme activity. PE does not increase the release of [14C]adenine-labeled compounds into the media. Approximately 13% of soluble 14C counts was found in the media of chondrocytes treated with PE while 18% of counts was released in the presence of HP alone. We have demonstrated a factor or factors present in FCS, HS, and an acid-ethanol extract of human platelets which represent(s) the first known physiologic modulators of PPi production in articular cartilage and may increase PPi production without affecting NTPPPH activity.
关节软骨中无机焦磷酸（PPi）的紊乱产生被认为在二水焦磷酸钙沉积病以及可能的骨关节炎发病机制中起重要作用。我们之前已经表明，添加到猪关节软骨外植体培养基中的胎牛血清会增加PPi向周围培养基中的分泌。我们通过研究成人血清（HS）、成人血浆衍生血清（HP）和人血小板酸醇提取物（PE）对软骨器官培养中PPi产生的影响，来检测这种PPi刺激活性。培养48小时后，10%的HS使PPi产生增加1.4倍，而在含有10% HP的培养基中培养的软骨产生的PPi并不比仅在培养基中培养的软骨多。在低浓度HP存在的情况下，PE在48小时时刺激PPi产生平均增加2倍，单独使用时无作用。它似乎不会上调胞外酶核苷三磷酸焦磷酸水解酶（NTPPPH）的活性，也不会促进酶底物释放到细胞外空间。暴露于0.5% HP和PE的软骨具有1.51±0.36单位的NTPPPH活性，而仅暴露于0.5% HP的软骨具有1.52±0.41单位的酶活性。PE不会增加[14C]腺嘌呤标记化合物向培养基中的释放。在用PE处理的软骨细胞培养基中发现约13%的可溶性14C计数，而仅在HP存在时释放18%的计数。我们已经证明了胎牛血清、成人血清和人血小板酸乙醇提取物中存在一种或多种因子，这些因子是关节软骨中PPi产生的首批已知生理调节剂，并且可能在不影响NTPPPH活性的情况下增加PPi产生。
