CHONDROCYTE ECTO-ENZYME PYROPHOSPHATE METABOLISM

过去十年的研究表明， 关节内产生无机焦磷酸盐（PPi）是一种 焦磷酸钙二水合物重要代谢缺陷 （CPPD）和碱性磷酸钙（BCP）晶体沉积 关节病和可能的骨关节炎。 卡宾枪一直是 被确定为关节PPi过量的可能来源， 实验表明，分离的软骨细胞，但不是 滑膜来源的细胞，可以解释所有的PPi释放， 体外软骨。 PPi活性降低 产生胞外酶，核苷酸磷酸水解酶 （NPPH），与滑膜中观察到的异常相关 液体PPi浓度。 这可能是发病的重要性。 软骨细胞单层培养模型的建立 细胞外PPi和NPPH的加工， 人关节中PPi和NPPH活性的流体测量。 这一模型为研究植物在植物生长发育过程中的作用提供了一个理想的系统 软骨细胞外-NPPH作用在软骨细胞PPi加工中。 将软骨细胞NPPH纯化并用于制备兔软骨细胞 抗血清 抗体可以选择性地阻断NPPH活性， 因此，确定细胞外PPi的加工是否可以 与外NPPH作用解偶联。 其他实验包括 建议确定主要代谢来源 软骨细胞PPi和机制的自发加工 细胞外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.