Increased expression of nerve growth factor (NGF) and high affinity NGF receptor (p140 TrkA) in human osteoarthritic chondrocytes
Increased expression of nerve growth factor (NGF) and high affinity NGF receptor (p140 TrkA) in human osteoarthritic chondrocytes
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DOI：
10.1093/rheumatology/41.12.1413
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发表时间：
2002-12-01
期刊：
影响因子：
5.5
通讯作者：
Lapadula, G
中科院分区：
文献类型：
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作者：
Iannone, F;De Bari, C;Lapadula, G
Objective.本研究旨在观察正常人和骨关节炎软骨细胞上神经生长因子（NGF）及其受体p140 TrkA的表达。我们招募了12名接受手术膝关节置换术的骨关节炎（OA）患者。关节软骨被分成两个区域，在宏观和组织学上显示了最低（MIN）和最高（MAX）程度的骨关节炎损伤。从三个健康供体获得额外的软骨标本。通过酶消化分离软骨细胞，并新鲜处理用于NGF蛋白、Trk A检测和mRNA提取。通过逆转录-聚合酶链反应（RT-PCR）测定NGF-β mRNA。通过免疫荧光和流式细胞术分析评估NGF-β和TrkA的表达。在正常和骨关节炎软骨细胞中检测到NGF-β特异性mRNA。在正常软骨细胞中，NGF-β蛋白水平较低，在MIN骨关节炎软骨中增加，在MAX骨关节炎软骨中进一步增强。同样，TrkA在正常软骨细胞上几乎不表达，而在骨关节炎软骨细胞上的表达随着解剖损伤程度的增加而逐渐增加。这是第一项研究表明，人类软骨细胞合成NFG-β，并在其表面表达高亲和力的NGFR（p140 TrkA）。值得注意的是，骨关节炎软骨细胞中的NGF-β和TrkA上调，表明NGF在OA的病理生理学中的作用。我们可以推测，像其他生长因子一样，在骨关节炎过程中，NGF刺激软骨细胞代谢。
Objective. We aimed to investigate the expression of nerve growth factor (NGF) and high affinity NGF receptor (p140 TrkA) on chondrocytes from human healthy and osteoarthritic cartilage.Methods. We recruited 12 patients with osteoarthritis (OA) undergoing surgical knee replacement. Articular cartilage was split into two zones showing macroscopically and histologically the lowest (MIN) and highest (MAX) degree of osteoarthritic damage. Additional specimens of cartilage were obtained from three healthy donors. Chondrocytes were isolated by enzymatic digestion and freshly processed for NGF protein, Trk A detection and mRNA extraction. NGF-beta mRNA was determined by a reverse transcriptase-polymerase chain reaction (RT-PCR). NGF-beta and TrkA expression was evaluated by immunofluorescence and flow cytometry analysis.Results. NGF-beta-specific mRNA was detected in normal and osteoarthritic chondrocytes. NGF-beta protein levels were low in normal chondrocytes, increased in MIN osteoarthritic cartilage and further enhanced in MAX osteoarthritic cartilage. Likewise, TrkA was scarcely expressed on normal chondrocytes and progressively increased on osteoarthritic chondrocytes based on the extent of anatomic damage.Conclusions. This is the first study showing that human chondrocytes synthesize NFG-beta and express on their surface the high affinity NGFR (p140 TrkA). Of note, NGF-beta and TrkA were upregulated in osteoarthritic chondrocytes suggesting a role of NGF in the pathophysiology of OA. We can speculate that NGF, like other growth factors, stimulates chondrocyte metabolism in the osteoarthritic process.