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Suppression of p38α MAPK Signaling in Osteoblast Lineage Cells Impairs Bone Anabolic Action of Parathyroid Hormone.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Thouverey, Cyril Caverzasio, Joseph |
| Copyright Year | 2016 |
| 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. |
| File Format | PDF HTM / HTML |
| DOI | 10.1002/jbmr.2762 |
| PubMed reference number | 26643857 |
| Journal | Medline |
| Volume Number | 31 |
| Issue Number | 5 |
| Alternate Webpage(s) | http://onlinelibrary.wiley.com/store/10.1002/jbmr.2762/asset/supinfo/jbmr2762-sup-0001-SuppData-S1.pdf?s=dc044b725820028165b4cd8a50ee274f167ac4f9&v=1 |
| Alternate Webpage(s) | https://doi.org/10.1002/jbmr.2762 |
| Journal | Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
