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Suppression of p38α MAPK Signaling in Osteoblast Lineage Cells Impairs Bone Anabolic Action of Parathyroid Hormone
Author(s) -
Thouverey Cyril,
Caverzasio Joseph
Publication year - 2016
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.2762
Subject(s) - endocrinology , medicine , parathyroid hormone , osteoblast , rankl , bone resorption , osteocalcin , anabolism , bone remodeling , mapk/erk pathway , p38 mitogen activated protein kinases , chemistry , signal transduction , activator (genetics) , biology , receptor , microbiology and biotechnology , alkaline phosphatase , calcium , biochemistry , enzyme , in vitro
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.