title: Suppression of p38α MAPK Signaling in Osteoblast Lineage Cells Impairs Bone Anabolic Action of Parathyroid Hormone.
abstract: Intermittent parathyroid hormone administration (iPTH) increases bone mass and strength by stimulating osteoblast number and activity. PTH exerts its anabolic effects through cAMP/protein kinase A (PKA) signaling pathway in mature osteoblasts and osteocytes. Here, we show that inactivation of the p38α MAPK-encoding gene with the use of an osteocalcin-cre transgene prevents iPTH bone anabolic action. Indeed, iPTH fails to increase insulin-like growth factor 1 expression, osteoblast number and activity, and bone formation in mice lacking p38α in osteoblasts and osteocytes. Moreover, iPTH-induced expression of receptor activator of NF-κB ligand (RANKL) and subsequent increased bone resorption are suppressed in those mice. Finally, we found that PTH activates p38α MAPK downstream of cAMP/PKA signaling pathway in mature osteoblasts. Our findings identify p38α MAPK as a key component of PTH signaling in osteoblast lineage cells and highlight its requirement in iPTH osteoanabolic activity. © 2015 American Society for Bone and Mineral Research.
authors.affiliation: Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Cyril
authors.initials: C
authors.lastname: Thouverey
authors.affiliation: Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Joseph
authors.initials: J
authors.lastname: Caverzasio
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism*; D010011:Osteocytes / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D010281:Parathyroid Hormone; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: BONE ANABOLISM; BONE REMODELING; OSTEOBLASTS; PARATHYROID HORMONE; p38α MAPK