Title | Mitogen-activated protein kinase pathways in osteoblasts. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Greenblatt MB, Shim J-H, Glimcher LH |
Journal | Annu Rev Cell Dev Biol |
Volume | 29 |
Pagination | 63-79 |
Date Published | 2013 |
ISSN | 1530-8995 |
Keywords | Animals, Humans, MAP Kinase Signaling System, Mitogen-Activated Protein Kinases, Osteoblasts, Osteogenesis |
Abstract | Mitogen-activated protein kinases (MAPKs) are ancient signal transducers well characterized as mediators of inflammation and neoplastic transformation. Recent work has expanded our understanding of their developmental functions, particularly in the regulation of bone mass via control of osteoblast differentiation. Here, we review the functions of MAPK pathways in osteoblasts, including a consideration of MAPK substrates. In particular, MAPKs function to regulate the key transcriptional mediators of osteoblast differentiation, with ERK and p38 MAPKs phosphorylating RUNX2, the master regulator of osteoblast differentiation. ERK also activates RSK2, which in turn phosphorylates ATF4, a transcriptional regulator of late-stage osteoblast synthetic functions. The MAP3Ks and MAP2Ks upstream of MAPKs have also been investigated, and significant differences have been found in the wiring of MAPK pathways in osteoblasts relative to other tissues. Thus, the investigation of MAPKs in osteoblasts has both revealed critical mechanisms for the maintenance of bone mass and added to our understanding of how the individual components of MAPK pathways function in concert in a complex in vivo system. |
DOI | 10.1146/annurev-cellbio-101512-122347 |
Alternate Journal | Annu Rev Cell Dev Biol |
PubMed ID | 23725048 |
Grant List | HD055601 / HD / NICHD NIH HHS / United States T32 CA070083 / CA / NCI NIH HHS / United States |
Related Faculty:
Matthew B. Greenblatt, M.D., Ph.D.