Reduced expression and function of bone morphogenetic protein-2 in bones of Fgf2 null mice

Takahiro Naganawa, Liping Xiao, J. D. Coffin, Thomas C Doetschman, Maria Giovanna Sabbieti, Dimitrios Agas, Marja M. Hurley

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Disruption of the fibroblast growth factor 2 (FGF-2) gene results in reduced bone mass in mice and impairs expression of bone morphogenic protein-2 (BMP-2) an important mediator of osteoblast and osteoclast differentiation. Since the relationship between FGF-2 and BMP-2 in bone remodeling has not been fully determined, in this study we examined whether endogenous FGF-2 was necessary for maximal effect of BMP-2 on periosteal bone formation in vivo and bone nodule formation and osteoclast formation in vitro in Fgf2-/- mice. We showed that BMP-2 significantly increased periosteal bone formation by 57% in Fgf2+/+ mice but the changes were not significant in Fgf2-/- littermates. In line with these results we found no significant increase in alkaline phosphatase positive (ALP) activity in calvarial osteoblasts or ALP mineralized colonies in stromal cultures from Fgf2-/- mice after BMP-2 treatment. Moreover, BMP-2 induced osteoclast formation was also impaired in marrow stromal cultures from Fgf2-/- mice. Interestingly, BMP-2 induced nuclear accumulation of the runt related transcription factor (Runx2) was markedly impaired in osteoblasts from Fgf2-/- mice. Examination of the effect of loss of FGF-2 on BMP-2 signaling pathway showed that BMP-2 caused a similar induction of phospho-Smad1/5/8 within 30 min in calvarial osteoblasts from both genotypes. In contrast BMP-2-induced p42/44 MAPK was reduced in Fgf2-/- mice. These findings strongly demonstrated that endogenous FGF-2 is important in the maximal responses of BMP-2 in bone and that this may be dependent on the p42/44 MAPK signaling pathway and downstream modulation of Runx2.

Original languageEnglish (US)
Pages (from-to)1975-1988
Number of pages14
JournalJournal of Cellular Biochemistry
Volume103
Issue number6
DOIs
StatePublished - Apr 15 2008

Fingerprint

Bone Morphogenetic Protein 2
Bone
Bone and Bones
Fibroblast Growth Factor 2
Proteins
Osteoblasts
Osteoclasts
Osteogenesis
Mitogen-Activated Protein Kinase 1
Alkaline Phosphatase
Bone Remodeling

Keywords

  • BMP-2
  • Fgf2 null mice
  • MAPKinase
  • Osteoblast

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Reduced expression and function of bone morphogenetic protein-2 in bones of Fgf2 null mice. / Naganawa, Takahiro; Xiao, Liping; Coffin, J. D.; Doetschman, Thomas C; Sabbieti, Maria Giovanna; Agas, Dimitrios; Hurley, Marja M.

In: Journal of Cellular Biochemistry, Vol. 103, No. 6, 15.04.2008, p. 1975-1988.

Research output: Contribution to journalArticle

Naganawa, Takahiro ; Xiao, Liping ; Coffin, J. D. ; Doetschman, Thomas C ; Sabbieti, Maria Giovanna ; Agas, Dimitrios ; Hurley, Marja M. / Reduced expression and function of bone morphogenetic protein-2 in bones of Fgf2 null mice. In: Journal of Cellular Biochemistry. 2008 ; Vol. 103, No. 6. pp. 1975-1988.
@article{c43983dee5034c1d811f53974a7b2e16,
title = "Reduced expression and function of bone morphogenetic protein-2 in bones of Fgf2 null mice",
abstract = "Disruption of the fibroblast growth factor 2 (FGF-2) gene results in reduced bone mass in mice and impairs expression of bone morphogenic protein-2 (BMP-2) an important mediator of osteoblast and osteoclast differentiation. Since the relationship between FGF-2 and BMP-2 in bone remodeling has not been fully determined, in this study we examined whether endogenous FGF-2 was necessary for maximal effect of BMP-2 on periosteal bone formation in vivo and bone nodule formation and osteoclast formation in vitro in Fgf2-/- mice. We showed that BMP-2 significantly increased periosteal bone formation by 57{\%} in Fgf2+/+ mice but the changes were not significant in Fgf2-/- littermates. In line with these results we found no significant increase in alkaline phosphatase positive (ALP) activity in calvarial osteoblasts or ALP mineralized colonies in stromal cultures from Fgf2-/- mice after BMP-2 treatment. Moreover, BMP-2 induced osteoclast formation was also impaired in marrow stromal cultures from Fgf2-/- mice. Interestingly, BMP-2 induced nuclear accumulation of the runt related transcription factor (Runx2) was markedly impaired in osteoblasts from Fgf2-/- mice. Examination of the effect of loss of FGF-2 on BMP-2 signaling pathway showed that BMP-2 caused a similar induction of phospho-Smad1/5/8 within 30 min in calvarial osteoblasts from both genotypes. In contrast BMP-2-induced p42/44 MAPK was reduced in Fgf2-/- mice. These findings strongly demonstrated that endogenous FGF-2 is important in the maximal responses of BMP-2 in bone and that this may be dependent on the p42/44 MAPK signaling pathway and downstream modulation of Runx2.",
keywords = "BMP-2, Fgf2 null mice, MAPKinase, Osteoblast",
author = "Takahiro Naganawa and Liping Xiao and Coffin, {J. D.} and Doetschman, {Thomas C} and Sabbieti, {Maria Giovanna} and Dimitrios Agas and Hurley, {Marja M.}",
year = "2008",
month = "4",
day = "15",
doi = "10.1002/jcb.21589",
language = "English (US)",
volume = "103",
pages = "1975--1988",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - Reduced expression and function of bone morphogenetic protein-2 in bones of Fgf2 null mice

AU - Naganawa, Takahiro

AU - Xiao, Liping

AU - Coffin, J. D.

AU - Doetschman, Thomas C

AU - Sabbieti, Maria Giovanna

AU - Agas, Dimitrios

AU - Hurley, Marja M.

PY - 2008/4/15

Y1 - 2008/4/15

N2 - Disruption of the fibroblast growth factor 2 (FGF-2) gene results in reduced bone mass in mice and impairs expression of bone morphogenic protein-2 (BMP-2) an important mediator of osteoblast and osteoclast differentiation. Since the relationship between FGF-2 and BMP-2 in bone remodeling has not been fully determined, in this study we examined whether endogenous FGF-2 was necessary for maximal effect of BMP-2 on periosteal bone formation in vivo and bone nodule formation and osteoclast formation in vitro in Fgf2-/- mice. We showed that BMP-2 significantly increased periosteal bone formation by 57% in Fgf2+/+ mice but the changes were not significant in Fgf2-/- littermates. In line with these results we found no significant increase in alkaline phosphatase positive (ALP) activity in calvarial osteoblasts or ALP mineralized colonies in stromal cultures from Fgf2-/- mice after BMP-2 treatment. Moreover, BMP-2 induced osteoclast formation was also impaired in marrow stromal cultures from Fgf2-/- mice. Interestingly, BMP-2 induced nuclear accumulation of the runt related transcription factor (Runx2) was markedly impaired in osteoblasts from Fgf2-/- mice. Examination of the effect of loss of FGF-2 on BMP-2 signaling pathway showed that BMP-2 caused a similar induction of phospho-Smad1/5/8 within 30 min in calvarial osteoblasts from both genotypes. In contrast BMP-2-induced p42/44 MAPK was reduced in Fgf2-/- mice. These findings strongly demonstrated that endogenous FGF-2 is important in the maximal responses of BMP-2 in bone and that this may be dependent on the p42/44 MAPK signaling pathway and downstream modulation of Runx2.

AB - Disruption of the fibroblast growth factor 2 (FGF-2) gene results in reduced bone mass in mice and impairs expression of bone morphogenic protein-2 (BMP-2) an important mediator of osteoblast and osteoclast differentiation. Since the relationship between FGF-2 and BMP-2 in bone remodeling has not been fully determined, in this study we examined whether endogenous FGF-2 was necessary for maximal effect of BMP-2 on periosteal bone formation in vivo and bone nodule formation and osteoclast formation in vitro in Fgf2-/- mice. We showed that BMP-2 significantly increased periosteal bone formation by 57% in Fgf2+/+ mice but the changes were not significant in Fgf2-/- littermates. In line with these results we found no significant increase in alkaline phosphatase positive (ALP) activity in calvarial osteoblasts or ALP mineralized colonies in stromal cultures from Fgf2-/- mice after BMP-2 treatment. Moreover, BMP-2 induced osteoclast formation was also impaired in marrow stromal cultures from Fgf2-/- mice. Interestingly, BMP-2 induced nuclear accumulation of the runt related transcription factor (Runx2) was markedly impaired in osteoblasts from Fgf2-/- mice. Examination of the effect of loss of FGF-2 on BMP-2 signaling pathway showed that BMP-2 caused a similar induction of phospho-Smad1/5/8 within 30 min in calvarial osteoblasts from both genotypes. In contrast BMP-2-induced p42/44 MAPK was reduced in Fgf2-/- mice. These findings strongly demonstrated that endogenous FGF-2 is important in the maximal responses of BMP-2 in bone and that this may be dependent on the p42/44 MAPK signaling pathway and downstream modulation of Runx2.

KW - BMP-2

KW - Fgf2 null mice

KW - MAPKinase

KW - Osteoblast

UR - http://www.scopus.com/inward/record.url?scp=41849139669&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41849139669&partnerID=8YFLogxK

U2 - 10.1002/jcb.21589

DO - 10.1002/jcb.21589

M3 - Article

C2 - 17955502

AN - SCOPUS:41849139669

VL - 103

SP - 1975

EP - 1988

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 6

ER -