Stöve Johannes, Gremmes Christina, Günther Klaus Peter, Scharf Hanns-Peter, Schwarz Markus
Department of Orthopaedic Surgery, Faculty of Clinical Medicine, Mannheim University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Biomed Pharmacother. 2006 Dec;60(10):644-7. doi: 10.1016/j.biopha.2006.09.005. Epub 2006 Oct 24.
The aim of this study was to analyze metabolic activity of osteoarthritic chondrocytes in correlation with radiographic, histologic and gene expression data. Six patients with osteoarthritis (OA) of the knee were analyzed clinically and radiographically (Kellgren and Lawrence, K&L). During total knee replacement surgery cartilage samples from the medial and lateral condyles and tibial plateaus were separately harvested. Specimen were analyzed histologically (Mankin Score) and total RNA was extracted. Steady state levels of stromelysin (MMP-3), aggrecan (AGG) and the house-keeping gene beta-actin were measured using quantitative PCR. In order to estimate metabolic activity chondrocytes were cultured in alginate beads and proteoglycan content was measured after 1 week. PG content in cultures was dependent from degradation status of cartilage (medial compartments 20.4 +/- 0.83 ng/ng, lateral compartments 29.9 +/- 3.0 ng/ng P < 0.01). We found a positive correlation of PG content in cultures with Mankin's grading (r = 0.79; P < 0.01) and with K&L scoring (r = 0.57; P = 0.05). There was a considerable variation of expression levels of MMP-3 and AGG. PG metabolism of cultured chondrocytes correlated only with the macroscopic and microscopic degradation status of cartilage. Gene expression showed a high variability and no correlation to PG metabolism indicating a more complex regulation.
本研究的目的是分析骨关节炎软骨细胞的代谢活性，并将其与放射学、组织学和基因表达数据相关联。对6例膝关节骨关节炎（OA）患者进行了临床和放射学分析（Kellgren和Lawrence，K&L分级）。在全膝关节置换手术期间，分别从内侧和外侧髁以及胫骨平台采集软骨样本。对样本进行组织学分析（Mankin评分）并提取总RNA。使用定量PCR测量基质溶解素（MMP-3）、聚集蛋白聚糖（AGG）和管家基因β-肌动蛋白的稳态水平。为了评估代谢活性，将软骨细胞培养在藻酸盐珠中，并在1周后测量蛋白聚糖含量。培养物中的PG含量取决于软骨的降解状态（内侧隔室为20.4±0.83 ng/ng，外侧隔室为29.9±3.0 ng/ng，P<0.01）。我们发现培养物中PG含量与Mankin分级呈正相关（r = 0.79；P<0.01），与K&L评分呈正相关（r = 0.57；P = 0.05）。MMP-3和AGG的表达水平存在相当大的差异。培养的软骨细胞的PG代谢仅与软骨的宏观和微观降解状态相关。基因表达显示出高度变异性，与PG代谢无相关性，表明存在更复杂的调控。
