CHONDROCYTE ECTO-ENZYME PYROPHOSPHATE METABOLISM

过去十年的研究表明，高得不寻常的 关节内生产无机焦磷酸(PPI)是一种 二水焦磷酸钙的重要代谢缺陷 (CPPD)和碱性磷酸钙(BCP)晶体沉积 关节病，可能还有骨性关节炎。软骨已经被 被确定为关节PPI过高的可能来源，以及最近 实验表明，分离的软骨细胞，但不是 滑膜来源的细胞，可以解释所有PPI从 软骨细胞的体外培养。PPI活动异常 产生胞外酶，核苷酸磷酸水解酶 (NPPH)，与观察到的滑膜异常有很好的相关性 液体PPI浓度。这可能是重要的致病因素。 自发性软骨细胞单层培养模型的建立 再生滑膜的细胞外PPI和NPPH精加工 人体关节PPI和NPPH活性的流体测量。 这个模型提供了一个理想的系统，可以在其中研究 软骨细胞胞外NPPH在软骨细胞PPI表达中的作用。 软骨细胞NPPH将被提纯并用于制备兔 抗血清。一种抗体可以选择性地阻断NPPH活性并 因此，确定细胞外PPI精细化是否可以 从ecto-NPPH作用中解偶联。其他实验包括 建议确定主要代谢来源(S) 软骨细胞PPI及其自发形成机制 软骨细胞胞外PPI和NPPH。

Research in the last decade has revealed that abnormally high intra-articular production of inorganic pyrophosphate (PPi) is an important metabolic defect in calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP) crystal deposition arthropathies and possibly osteoarthritis. Cartilage has been identified as a probable source of excess articular PPi, and recent experiments have shown that the isolated chondrocyte, but not synovial derived cells, can account for all the PPi released from cartilage in vitro. Abnormalities in the activity of the PPi generating ecto-enzyme, nucleotide phyrophosphohydrolase (NPPH), correlate well with the observed abnomalities in synovial fluid PPi concentration. This may be of pathogenetic importance. A chondrocyte monolayer culture model of spontaneous extracellular PPi and NPPH elaboration which reproduces synovial fluid measurements of PPi and NPPH activity in human joints. This model furnish an ideal system in which to study the role of chondrocyte ecto-NPPH action in chondrocyte PPi elaboration. Chondrocyte NPPH will be purified and used to prepared rabbit antisera. An antibody could selectively block NPPH activity and therefore determine if extracellular PPi elaboration can be uncoupled from ecto-NPPH action. Additional experiments are proposed to determine the major metabolic source(s) of chondrocyte PPi and mechanisms of spontaneous elaboration of extracellular PPi and NPPH by chondrocytes.