| First Author | Gao Y | Year | 2008 |
| Journal | Cell Metab | Volume | 8 |
| Issue | 2 | Pages | 132-45 |
| PubMed ID | 18680714 | Mgi Jnum | J:140132 |
| Mgi Id | MGI:3811972 | Doi | 10.1016/j.cmet.2008.07.001 |
| Citation | Gao Y, et al. (2008) T cells potentiate PTH-induced cortical bone loss through CD40L signaling. Cell Metab 8(2):132-45 |
| abstractText | 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-kappaB 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. |
