T cell activation induces human osteoclast formation via receptor activator of nuclear factor κB ligand-dependent and -independent mechanisms

M. N. Weitzmann, S. Cenci, L. Rifas, J. Haug, J. Dipersio, R. Pacifici

Research output: Contribution to journalArticle

Abstract

In unstimulated conditions, osteoclast (OC) formation is regulated by stromal cell production of the key osteoclastogenic factors receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). However, the mechanisms of accelerated osteoclastogenesis and bone loss characteristic of inflammatory conditions are poorly understood but appear to involve T cells. In addition, the mechanism by which OCs arise spontaneously in cultures of peripheral blood mononuclear cells in the absence of stromal cells or added cytokines remains unclear. Using a stromal cell free human osteoclast generating system, we investigated the ability of activated T cells to support osteoclastogenesis. We show that when activated by phytohemagglutinin-P (PHA), T cells (both CD4+ and CD8+) stimulate human OC formation in vitro. Although both soluble M-CSF and RANKL were detected in activated T cell supernatants, the presence of M-CSF was not essential for macrophage survival or RANKL-dependent osteoclast formation, suggesting that other soluble T cell-derived factors were capable of substituting for this cytokine. We also found that saturating concentrations of osteoprotegerin (OPG) failed to neutralize 30% of the observed OC formation and that T cell conditioned medium (CM) could superinduce osteoclastogenesis in cultures of purified monocytes maximally stimulated by RANKL and M-CSF. Together, these data suggest that activated T cells support osteoclastogenesis via RANKL-dependent and -independent mechanisms. Although not relevant for T cell-induced osteoclastogenesis, secretion of soluble M-CSF is a previously undescribed property of activated T cells.

Original languageEnglish
Pages (from-to)328-337
Number of pages10
JournalJournal of Bone and Mineral Research
Volume16
Issue number2
Publication statusPublished - 2001

Keywords

  • Macrophage colony-stimulating factor
  • Osteoclast
  • Osteoprotegerin
  • Receptor activator of nuclear factor κB ligand
  • T cell

ASJC Scopus subject areas

  • Surgery

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