| First Author | Thouverey C | Year | 2015 |
| Journal | Endocrinology | Volume | 156 |
| Issue | 12 | Pages | 4377-87 |
| PubMed ID | 26441240 | Mgi Jnum | J:232744 |
| Mgi Id | MGI:5780016 | Doi | 10.1210/en.2015-1669 |
| Citation | Thouverey C, et al. (2015) Ablation of p38alpha MAPK Signaling in Osteoblast Lineage Cells Protects Mice From Bone Loss Induced by Estrogen Deficiency. Endocrinology 156(12):4377-87 |
| abstractText | Estrogen deficiency causes bone loss by increasing the number of bone-resorbing osteoclasts. Selective p38alpha MAPK inhibitors prevent bone-wasting effects of estrogen withdrawal but implicated mechanisms remain to be identified. Here, we show that inactivation of the p38alpha-encoding gene in osteoblast lineage cells with the use of an osteocalcin-cre transgene protects mice from ovariectomy-induced bone loss (a murine model of postmenopausal osteoporosis). Ovariectomy fails to induce bone loss, increase bone resorption, and stimulate receptor activator of nuclear factor kappaB ligand and IL-6 expression in mice lacking p38alpha in osteoblasts and osteocytes. Finally, TNFalpha or IL-1, which are osteoclastogenic cytokines overproduced in the bone marrow under estrogen deficiency, can activate p38alpha signaling in osteoblasts, but those cytokines cannot enhance Rankl and Il6 expressions or increase osteoclast formation in p38a-deficient osteoblast cultures. These findings demonstrate that p38alpha MAPK signaling in osteoblast lineage cells mediates ovariectomy-induced bone loss by up-regulating receptor activator of nuclear factor kappaB ligand and IL-6 production. |
