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Publication : Ras signaling regulates osteoprogenitor cell proliferation and bone formation.

First Author  Papaioannou G Year  2016
Journal  Cell Death Dis Volume  7
Issue  10 Pages  e2405
PubMed ID  27735946 Mgi Jnum  J:312644
Mgi Id  MGI:6791869 Doi  10.1038/cddis.2016.314
Citation  Papaioannou G, et al. (2016) Ras signaling regulates osteoprogenitor cell proliferation and bone formation. Cell Death Dis 7(10):e2405
abstractText  During endochondral bone development, osteoblasts are continuously differentiated from locally residing progenitor cells. However, the regulation of such endogenous osteoprogenitor cells is still poorly understood mainly due to the difficulty in identifying such cells in vivo. In this paper, we genetically labeled different cell populations of the osteoblast linage using stage-specific, tamoxifen-inducible Cre transgenic mice to investigate their responses to a proliferative stimulus. We have found that overactivation of Kras signaling in type II collagen-positive, immature osteoprogenitor cells, but not in mature osteoblasts, substantially increases the number of their descendant stromal cells and mature osteoblasts, and subsequently increases bone mass. This effect was mediated by both, the extracellular signal-regulated kinase (ERK) and phosphoinositide 3 kinase (PI3K), pathways. Thus we demonstrate that Ras signaling stimulates proliferation of immature osteoprogenitor cells to increase the number of their osteoblastic descendants in a cell-autonomous fashion.
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