Ovariectomy disregulates osteoblast and osteoclast formation through the T-cell receptor CD40 ligand

Academic Article

Abstract

  • The bone loss induced by ovariectomy (ovx) has been linked to increased production of osteoclastogenic cytokines by bone marrow cells, including T cells and stromal cells (SCs). It is presently unknown whether regulatory interactions between these lineages contribute to the effects of ovx in bone, however. Here, we show that the T-cell costimulatory molecule CD40 ligand (CD40L) is required for ovx to expand SCs; promote osteoblast proliferation and differentiation; regulate the SC production of the osteoclastogenic factors macrophage colony-stimulating factor, receptor activator of nuclear factor-κ ligand, and osteoprotegerin; and upregulate osteoclast formation. CD40L is also required for ovx to activate T cells and stimulate their production of TNF. Accordingly, ovx fails to promote bone loss and increase bone resorption in mice depleted of T cells or lacking CD40L. Therefore, cross-talk between T cells and SCs mediated by CD40L plays a pivotal role in the disregulation of osteoblastogenesis and osteoclastogenesis induced by ovx.
  • Digital Object Identifier (doi)

    Author List

  • Li JY; Tawfeek H; Bedi B; Yang X; Adams J; Gao KY; Zayzafoon M; Weitzmann MN; Pacifici R
  • Start Page

  • 768
  • End Page

  • 773
  • Volume

  • 108
  • Issue

  • 2