Neutral proteases capable of proteoglycan digesting activity in osteoarthritic and normal human articular cartilage.
Neutral proteases capable of proteoglycan digesting activity in osteoarthritic and normal human articular cartilage.
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DOI：
10.1002/art.1780270310
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发表时间：
1984-03
影响因子：
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通讯作者：
J. Martel-Pelletier;J. Pelletier;J. Cloutier;D. Howell;L. Ghandur‐Mnaymneh;J. Woessner
中科院分区：
文献类型：
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作者：
J. Martel-Pelletier;J. Pelletier;J. Cloutier;D. Howell;L. Ghandur‐Mnaymneh;J. Woessner
蛋白酶被认为是骨关节炎（OA）软骨中基质蛋白聚糖逐渐消失的原因。内源性蛋白聚糖的消化中性蛋白酶在人骨关节炎软骨匀浆已被测量，并与正常年龄匹配的控制。在膝关节置换术时从16名患者和7名事故受害者中获得了软骨。从胫骨平台切割组织块;部分用于OA严重程度的组织学分级，部分均质化用于中性金属和丝氨酸蛋白酶活性的定量，基于内源性蛋白聚糖的消化产物的释放。总金属蛋白酶活性（潜伏加活性形式）升高3至10倍，在所有患病的软骨。这种升高在轻度疾病中已经很明显，但在中度至重度疾病的样本中最大。酶的活性形式是最高的糜烂中心和高原的边缘下降。蛋白聚糖的消化，从他们的组织中仅仅释放不同，证明了Sepharose-CL 2B上的色谱和大孔电泳。丝氨酸蛋白酶对蛋白多糖的活性远低于金属蛋白酶。平均活性在轻度疾病中最高，在重度疾病样品中下降，但这两组与对照组之间的差异无统计学意义。本研究结果与软骨中性金属蛋白酶参与骨关节炎蛋白多糖降解的假设一致。
Proteases have been postulated to account for the progressive disappearance of matrix proteoglycans in osteoarthritic (OA) cartilage. The digestion of endogenous proteoglycans by neutral proteases in human OA cartilage homogenates has been measured and compared with that of normal age-matched controls. Cartilage was obtained from 16 patients at the time of knee arthroplasty and from 7 accident victims. Tissue blocks were cut from the tibial plateau; part was used for histologic grading of the severity of OA and part was homogenized for the quantification of neutral metallo- and serine protease activities, based on the release of digested products from endogenous proteoglycans. Total metalloprotease activity (latent plus active forms) was elevated 3- to 10-fold in all diseased cartilage. This elevation was already significant in mild disease, but was greatest in samples of moderate to severe disease. The active form of the enzyme was highest at the center of erosions and decreased in the margins of the plateau. The digestion of proteoglycans, as distinct from their mere release from the tissue, was demonstrated by chromatography on Sepharose-CL2B and by large pore electrophoresis. Serine protease activity on proteoglycans was much lower than that of metalloprotease. The mean activity was highest in mild disease and declined in the severe disease samples, but the difference between these 2 groups and the controls was not statistically significant. The results of this study are consistent with the hypothesis that the neutral metalloproteases of cartilage are involved in the degradation of proteoglycans in osteoarthritis.