TY - JOUR
T1 - Stat1 controls postnatal bone formation by regulating fibroblast growth factor signaling in osteoblasts
AU - Xiao, Liping
AU - Naganawa, Takahiro
AU - Obugunde, Eneze
AU - Gronowicz, Gloria
AU - Ornitz, David M.
AU - Coffin, J. Douglas
AU - Hurley, Marja M.
PY - 2004/6/25
Y1 - 2004/6/25
N2 - Activation of the signal transducers and activators of transcription (STAT) pathway is important in fibroblast growth factor (FGF) modulation of chondrocyte proliferation and endochondral bone formation during embryogenesis. However, it is not known if the FGF/STAT signaling pathway is important for postnatal bone formation. To examine this, we have characterized a novel skeletal phenotype in Stat1-/- mice in which we find a significant increase in bone mineral density, bone mineral content, and other parameters of bone growth. The data show that osteoblasts derived from Stat1-/- mice have decreased expression of cell cycle inhibitor p21WAF/CIP and FGF receptor 3, a known negative regulator of chondrocyte proliferation. Interestingly, Stat1-/- osteoblasts showed increased expression of FGF18 in vivo and increased responsiveness to FGF18 in vitro. These results suggest a mechanism for the regulation of the osteoblast in which Stat1 functions not only to directly regulate the cell cycle but also to modify the repertoire of FGF receptor expression from a potentially inhibitory receptor, FGFR3 to a stimulatory receptor such as FGFR1 or FGFR2.
AB - Activation of the signal transducers and activators of transcription (STAT) pathway is important in fibroblast growth factor (FGF) modulation of chondrocyte proliferation and endochondral bone formation during embryogenesis. However, it is not known if the FGF/STAT signaling pathway is important for postnatal bone formation. To examine this, we have characterized a novel skeletal phenotype in Stat1-/- mice in which we find a significant increase in bone mineral density, bone mineral content, and other parameters of bone growth. The data show that osteoblasts derived from Stat1-/- mice have decreased expression of cell cycle inhibitor p21WAF/CIP and FGF receptor 3, a known negative regulator of chondrocyte proliferation. Interestingly, Stat1-/- osteoblasts showed increased expression of FGF18 in vivo and increased responsiveness to FGF18 in vitro. These results suggest a mechanism for the regulation of the osteoblast in which Stat1 functions not only to directly regulate the cell cycle but also to modify the repertoire of FGF receptor expression from a potentially inhibitory receptor, FGFR3 to a stimulatory receptor such as FGFR1 or FGFR2.
UR - http://www.scopus.com/inward/record.url?scp=3042600009&partnerID=8YFLogxK
U2 - 10.1074/jbc.M314323200
DO - 10.1074/jbc.M314323200
M3 - Article
C2 - 15073186
AN - SCOPUS:3042600009
SN - 0021-9258
VL - 279
SP - 27743
EP - 27752
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 26
ER -