The chitinase 3-like protein human cartilage glycoprotein 39 (HC-gp39) stimulates proliferation of human connective-tissue cells and activates both extracellular signal-regulated kinase- and protein kinase B-mediated signalling pathways.
Human cartilage glycoprotein 39 (HC-gp39) is a glycoprotein secreted by articular chondrocytes, synoviocytes and macrophages. Increased levels of HC-gp39 have been demonstrated in synovial fluids of patients with rheumatoid or osteoarthritis. The increased secretion of HC-gp39 under physiological and pathological conditions with elevated connective-tissue turnover suggests its involvement in the homoeostasis of these tissues. We report here that HC-gp39 promotes the growth of human synovial cells as well as skin and fetal lung fibroblasts. A dose-dependent growth stimulation was observed when each of the fibroblastic cell lines was exposed to HC-gp39 in a concentration range from 0.1 to 2 nM, which is similar to the effective dose of the well-characterized mitogen, insulin-like growth factor-1. At suboptimal concentrations, the two growth factors work in a synergistic fashion. The use of selective inhibitors of the mitogen-activated protein kinase and the protein kinase B (AKT) signalling pathways indicates that both are involved in mediating the mitogenic response to HC-gp39. Phosphorylation of both extracellular signal-regulated kinases 1/2 and AKT occurred in a dose- and time-dependent fashion upon addition of HC-gp39. Activation of these signalling pathways could also be demonstrated in human chondrocytes. Thus HC-gp39 initiates a signalling cascade in connective-tissue cells which leads to increased cell proliferation, suggesting that this protein could play a major role in the pathological conditions leading to tissue fibrosis.
Recklies
Anneliese D
AD
Joint Diseases Laboratory, Shriners Hospital for Children, 1529 Cedar Avenue, Montreal, QC, Canada H3G 1A6. arecklies@shriners.mcgill.ca
White
Chantal
C
Ling
Hua
H
D054392:Adipokines; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000071451:Chitinase-3-Like Protein 1; D002688:Chitinases / Q000502:physiology; D003239:Connective Tissue Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006023:Glycoproteins / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D037102:Lectins; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins; D011518:Proto-Oncogene Proteins; D007334:Insulin-Like Growth Factor I; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D002688:Chitinases