Interleukin‐1 and tumor necrosis factor stimulate the formation of human osteoclastlike cells in vitro

Johannes Pfeilschifter, Chantal Chenu, Andrew Bird, Gregory R. Mundy, David G. Roodman

Research output: Contribution to journalArticlepeer-review

395 Scopus citations


Interleukin‐1 (IL‐1) α and β and tumor necrosis factor (TNF) α and β are potent stimulators of bone resorption in vitro and in vivo. However, the mechanisms underlying this increased bone resorption have not been clearly defined. Increased bone resorption can result from increased activity of individual osteoclasts, increased numbers of osteoclasts, or both. Therefore, we have used a long‐term human marrow culture system that forms multinucleated cells (MNC) with the characteristics of osteoclasts to examine the effects of IL‐1 and TNF on osteoclast formation. Human recombinant IL‐1α and IL‐1β and human recombinant TNF‐α and TNF‐β stimulated MNC formation from 4‐ to 60‐fold. IL‐1α, IL‐1β, TNF‐α, and TNF‐β significantly increased MNC formation at very low concentrations: 2.5 × 10−13 M for IL‐1α and IL‐1β, 10−11 M for TNF‐α, and 10−10 M for TNF‐β In addition, these cytokines enhanced MNC formation in the presence of 1,25‐dihydroxyvitamin D3 [1,25‐(OH)2D3], a potent osteotropic factor that stimulates MNC formation by stimulating fusion of mononuclear precursor cells. Simultaneous addition of IL‐1 and TNF to the cultures resulted in a synergistic stimulation of MNC formation. These results suggest that: (1) IL‐1 and TNF stimulate bone resorption in part by increasing osteoclast formation and (2) an extremely low concentration of these factors can synergistically increase osteoclast formation in the absence of other factors, such as 1,25‐(OH)2D3. These data suggest that synergistic interactions among cytokines play an important role in maintaining bone cell activity in normal and pathologic states.

Original languageEnglish (US)
Pages (from-to)113-118
Number of pages6
JournalJournal of Bone and Mineral Research
Issue number1
StatePublished - Feb 1989

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine


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