Tumor necrosis factors α and β induce osteoblastic cells to stimulate osteoclastic bone resorption

B. M. Thomson, G. R. Mundy, T. J. Chambers

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461 Scopus citations

Abstract

Antigen- or mitogen-stimulated leukocytes release bone-resorbing activity into culture supernatants in vitro. Among the agents likely to be present in such supernatants are monocyte-derived tumor necrosis factor (TNF-α) and lymphocyte-derived tumor necrosis factor (TNF-β) (lymphotoxin), both of which have recently been shown to stimulate bone resorption in organ culture. To identify the mechanism of action of these agents, we compared bone resorption by isolated osteoclasts with bone resorption by osteoclasts cocultured with osteoblastic cells, and with bone resorption by oestoclasts incubated with supernatants from osteoblastic cells, in the presence and absence of recombinant TNF-α and TNF-β. We found that neither TNF-α nor TNF-β had any significant effect on bone resorption by isolated osteoclasts, but in the presence of osteoblasts the agents caused a twofold to threefold stimulation of bone resorption. A similar degree of stimulation was achieved by supernatants from osteoblasts incubated with TNF before addition to osteoclasts, compared with supernatants to which TNF were added after osteoblast incubation. These experiments suggest that TNF-α and TNF-β stimulate bone resorption through a primary effect on osteoblastic cells, which are induced by TNF to produce a factor that stimulates osteoclastic resorption. Half-maximal stimulation of resorption occurred at 1.5 x 10-10 M and 2.5 x 10-10 M for TNF-α and TNF-β, respectively. This degree of potency is comparable to that of parathyroid hormone, the major physiologic systemic regulator of bone resorption, and suggests that the TNF may exert a significant influence on osteoclastic bone resorption in vivo.

Original languageEnglish (US)
Pages (from-to)775-779
Number of pages5
JournalJournal of Immunology
Volume138
Issue number3
StatePublished - 1987
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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