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

Biochem J. 2002 Jul 1;365(Pt 1):119-26. doi: 10.1042/BJ20020075.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines
  • Cartilage, Articular / cytology
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / physiology*
  • Cell Division / drug effects
  • Cells, Cultured
  • Chitinase-3-Like Protein 1
  • Chitinases / physiology
  • Connective Tissue Cells / cytology
  • Connective Tissue Cells / drug effects
  • Connective Tissue Cells / physiology
  • Glycoproteins / pharmacology*
  • Glycoproteins / physiology
  • Humans
  • Insulin-Like Growth Factor I / pharmacology
  • Lectins
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction

Substances

  • Adipokines
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Glycoproteins
  • Lectins
  • Proto-Oncogene Proteins
  • Insulin-Like Growth Factor I
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Chitinases