Increased expression of nerve growth factor (NGF) and high affinity NGF receptor (p140 TrkA) in human osteoarthritic chondrocytes.

Abstract

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. 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. 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. 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.