Ovariectomy disregulates osteoblast and osteoclast formation through the T-cell receptor CD40 ligand
JY Li, H Tawfeek, B Bedi, X Yang… - Proceedings of the …, 2011 - National Acad Sciences
JY Li, H Tawfeek, B Bedi, X Yang, J Adams, KY Gao, M Zayzafoon, MN Weitzmann…
Proceedings of the National Academy of Sciences, 2011•National Acad SciencesThe 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 …
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 …
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-κB ligand, and osteoprotegerin; and up-regulate 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.
National Acad Sciences