Expression levels of gp130 in bone marrow stromal cells determine the magnitude of osteoclastogenic signals generated by IL-6-type cytokines

Charles A. O'Brien, Song Chang Lin, Teresita Bellido, Stavros C. Manolagas

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Interleukin-6 (IL-6)-type cytokines stimulate osteoclast formation by activating the glycoprotein 130 (gp130) receptor subunit on stromal/osteoblastic cells, which in turn leads to signal transducer and activator of transcription 3 (STAT3)-mediated expression of receptor activator of NF-κB ligand (RANKL). Based on evidence that gp130 expression is regulated by a variety of cytokines and hormones, we have determined here whether changes in gp130 levels directly contribute to the magnitude of the osteoclastogenic stimulus delivered by IL-6-type cytokines. To accomplish this, gp130 protein levels were modulated using a tetracycline-regulated expression system in a stromal/osteoblastic cell line, UAMS-32, which supports osteoclast formation. Removal of doxycycline from the culture medium elevated gp130 expression and increased the responsiveness of a STAT-responsive promoter-luciferase construct to IL-6 complexed with its soluble receptor (IL-6 + sIL-6R), but diminished the responsiveness to oncostatin M (OSM). IL-6 + sIL-6R-stimulated osteoclast formation was greater when osteoclast precursors were cocultured with the cells expressing elevated gp130 levels than when cells expressing low gp130 levels were used. However, increased gp130 levels reduced OSM-stimulated osteoclast formation. These results establish that the level of gp130 in stromal/osteoblastic cells directly modulates the magnitude of the osteoclastogenic response to IL-6-type cytokines such that an increase in gp130 increases the cellular responsiveness to IL-6 + sIL-6R but reduces responsiveness to OSM. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)532-541
Number of pages10
JournalJournal of Cellular Biochemistry
Volume79
Issue number4
DOIs
StatePublished - 2000
Externally publishedYes

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Mesenchymal Stromal Cells
Interleukin-6
Glycoproteins
Bone
Cytokines
Osteoclasts
Oncostatin M
Stromal Cells
Cells
Interleukin-6 Receptors
STAT3 Transcription Factor
Doxycycline
Tetracycline
Luciferases
Culture Media
Hormones
Ligands
Cell Line

Keywords

  • Oncostatin M
  • Osteoblast
  • RANKL
  • Receptor
  • STAT3

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Expression levels of gp130 in bone marrow stromal cells determine the magnitude of osteoclastogenic signals generated by IL-6-type cytokines. / O'Brien, Charles A.; Lin, Song Chang; Bellido, Teresita; Manolagas, Stavros C.

In: Journal of Cellular Biochemistry, Vol. 79, No. 4, 2000, p. 532-541.

Research output: Contribution to journalArticle

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