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Hepatocyte growth factor in osteoarthritis: when bone and cartilage decide to have a chat
Arthritis Res Ther volume 5, Article number: 162 (2003)
Recently, hepatocyte growth factor (HGF) has been identified by immunohistochemistry in cartilage and, more particularly, in the deep zone of human osteoarthritic (OA) cartilage. By investigating HGF expression in cartilage, we found that chondrocytes did not express HGF; however, they express the two truncated isoforms, namely HGF/NK1 and HGF/NK2. As the only other cells localized near the deep zone are osteoblasts from the subchondral bone plate, we hypothesized that they were expressing HGF. Indeed, we found that HGF was synthesized by osteoblasts from the subchondral bone plate. Moreover, OA osteoblasts produced five times more HGF than normal osteoblasts. Because prostaglandin E2 and proinflammatorycytokines such as IL-1 and IL-6 were involved in OA progression, we investigated whether these factors impact HGF produced by normal osteoblasts. Prostaglandin E2 was the only factor able to stimulateHGF synthesis. However, the addition of NS398, a selective inhibitor of cyclooxygenase-2, had no effect on HGF produced by OA osteoblasts. When investigating signaling routes that might be implicated in OA osteoblast-produced HGF, we found that protein kinase A and protein kinase C were involved. In summary, this study raises the hypothesis that the HGF found in articular cartilage is produced by osteoblasts, diffuses into the cartilage and may be implicated in the progression of OA. Furthermore, we investigated joints in HGF transgenic mice. We found that the subchondral bone was remodeled and that cartilage matrix was qualitatively different from the control mice. These results reinforced the idea of a role played by HGF in the joint.
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Reboul, P., Guévremont, M., Martel-Pelletier, J. et al. Hepatocyte growth factor in osteoarthritis: when bone and cartilage decide to have a chat. Arthritis Res Ther 5 (Suppl 3), 162 (2003). https://doi.org/10.1186/ar963