[PDF][PDF] T cells potentiate PTH-induced cortical bone loss through CD40L signaling
Cell metabolism, 2008•cell.com
Parathyroid hormone (PTH) promotes bone catabolism by targeting bone marrow (BM)
stromal cells (SCs) and their osteoblastic progeny. Here we show that a continuous infusion
of PTH that mimics hyperparathyroidism fails to induce osteoclast formation, bone
resorption, and cortical bone loss in mice lacking T cells. T cells provide proliferative and
survival cues to SCs and sensitize SCs to PTH through CD40 ligand (CD40L), a surface
molecule of activated T cells that induces CD40 signaling in SCs. As a result, deletion of T …
stromal cells (SCs) and their osteoblastic progeny. Here we show that a continuous infusion
of PTH that mimics hyperparathyroidism fails to induce osteoclast formation, bone
resorption, and cortical bone loss in mice lacking T cells. T cells provide proliferative and
survival cues to SCs and sensitize SCs to PTH through CD40 ligand (CD40L), a surface
molecule of activated T cells that induces CD40 signaling in SCs. As a result, deletion of T …
Summary
Parathyroid hormone (PTH) promotes bone catabolism by targeting bone marrow (BM) stromal cells (SCs) and their osteoblastic progeny. Here we show that a continuous infusion of PTH that mimics hyperparathyroidism fails to induce osteoclast formation, bone resorption, and cortical bone loss in mice lacking T cells. T cells provide proliferative and survival cues to SCs and sensitize SCs to PTH through CD40 ligand (CD40L), a surface molecule of activated T cells that induces CD40 signaling in SCs. As a result, deletion of T cells or T cell-expressed CD40L blunts the bone catabolic activity of PTH by decreasing bone marrow SC number, the receptor activator of nuclear factor-κB ligand (RANKL)/OSTEOPROTEGERN (OPG) ratio, and osteoclastogenic activity. Therefore, T cells play an essential permissive role in hyperparathyroidism as they influence SC proliferation, life span, and function through CD40L. T cell-SC crosstalk pathways may thus provide pharmacological targets for PTH-induced bone disease.
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