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Soluble glycoprotein 130 (gp130) attenuates OSM- and LIF-induced cartilage proteoglycan catabolism

W Hui1, M Bell, G Carroll

  • 1University Department of Medicine, University of Western Australia, Perth, Western Australia.

Cytokine
|February 15, 2000
PubMed

Insights

Soluble gp130 (sgp130) can reduce proteoglycan resorption in cartilage stimulated by Oncostatin M (OSM) and leukemia inhibitory factor (LIF). Anti-gp130 antibodies showed limited inhibition, suggesting sgp130

Area of Science:

  • Biochemistry and Molecular Biology
  • Cell Biology
  • Immunology

Background:

  • Oncostatin M (OSM) and Leukemia Inhibitory Factor (LIF) are cytokines with shared structural and genetic features.
  • Both OSM and LIF bind to the same receptor complex, comprising LIF receptor alpha chain (LIFRalpha) and gp130.
  • A soluble form of gp130 (sgp130) has been developed.

Purpose of the Study:

  • To investigate the potential of recombinant sgp130 and anti-gp130 antibodies to inhibit proteoglycan (PG) resorption induced by OSM and LIF in articular cartilage.
  • To explore the differential effects of sgp130 and anti-gp130 on cytokine-mediated cartilage metabolism.

Main Methods:

  • Articular cartilage explants were treated with OSM and LIF.
  • Recombinant soluble gp130 (sgp130) and anti-gp130 antibodies were used to assess their inhibitory effects on PG resorption.
  • Proteoglycan release was measured to quantify resorption.

Main Results:

  • High concentrations of sgp130 effectively attenuated PG resorption induced by both LIF and OSM.
  • Anti-gp130 antibodies demonstrated minimal and selective inhibition of OSM-stimulated PG release.
  • LIF-stimulated PG resorption was not significantly inhibited by anti-gp130 antibodies, possibly due to unimpeded LIF-LIFRalpha interaction and gp130 heterodimerization.

Conclusions:

  • Recombinant sgp130 and anti-gp130 antibodies can modulate cartilage proteoglycan metabolism in vitro.
  • sgp130 shows promise in inhibiting cytokine-induced cartilage degradation.
  • Further research is needed to determine the therapeutic potential of sgp130 in arthritis models and diseases.

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