[Fibroblast growth factor receptor 1 propagates estrogen and fluid shear stress driven proliferation and differentiation response in MC3T3-E1 cells].

Fluid shear stress (FSS) and estrogen exposure positively regulate bone metabolism. Fibroblast growth factor receptor 1 (FGFR1) plays a vital role in FSS-induced osteogenesis. An in vitro experiment with MC3T3-E1 cells combined with microarray analysis aided us in identification of the genes differentially expressed in response to FSS and highlighted the role of FGFR1 in this process. Both estrogen exposure and FSS increase methyl thiazol tetrazolium (MTT) values and alkaline phosphatase (ALP) activity, as well as the levels of Runt-related transcription factor 2 (Runx2) and osteocalcin (OCN). The effects of estrogen exposure and FSS were cumulative. Treatment with PD166866 inhibitor of the FGFR1 reduced the MTT values, increased ALP activity, and increased the levels of Runx2 and OCN. To investigate the regulation of FGFR1 signaling in stressed cells, a number of key components of the mitogen-activated protein kinase (MAPK) cascade were quantitatively examined. Neither estrogen nor FSS change the protein expression of extracellular signal-regulated kinase (ERK), Jun amino-terminal kinases (JNK) or p38, but positively influence their phosphorylation levels. Treatment with the FGFR1 inhibitor induced an increase in ERK phosphorylation levels only. In summary, estrogen exposure and FSS have a synergistic effect in osteogenesis. FGFR1 promotes osteoblast proliferation and inhibits the differentiation of osteoblasts. In MC3T3-E1 cells, FGFR1 signaling responds to independent and combined effects of estrogen and FSS. MAPK cascades participate in osteogenesis, but only the ERK signaling pathway responds to FGFR1.

Molecular gas in the halo fuels the growth of a massive cluster galaxy at high redshift.

The largest galaxies in the universe reside in galaxy clusters. Using sensitive observations of carbon monoxide, we show that the Spiderweb galaxy-a massive galaxy in a distant protocluster-is forming from a large reservoir of molecular gas. Most of this molecular gas lies between the protocluster galaxies and has low velocity dispersion, indicating that it is part of an enriched intergalactic medium. This may constitute the reservoir of gas that fuels the widespread star formation seen in earlier ultraviolet observations of the Spiderweb galaxy. Our results support the notion that giant galaxies in clusters formed from extended regions of recycled gas at high redshift.