PMID- 19049329
OWN - NLM
STAT- MEDLINE
DCOM- 20090518
LR  - 20181201
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Linking)
VI  - 24
IP  - 3
DP  - 2009 Mar
TI  - High cortical bone mass phenotype in betacellulin transgenic mice is EGFR 
      dependent.
PG  - 455-67
LID - 10.1359/jbmr.081202 [doi]
AB  - Signaling through the epidermal growth factor receptor (EGFR) by ligands such as 
      epidermal growth factor (EGF), transforming growth factor alpha (TGFA), and 
      amphiregulin (AREG) has been reported to have effects on skeletal growth. The 
      role of betacellulin (BTC), another EGFR ligand, in skeletal development and bone 
      metabolism is unknown. In previous experiments, transgenic mice overexpressing 
      BTC ubiquitously under the control of the chicken beta-actin promoter (BTC-tg) 
      exhibited stunted growth and disproportionately sized long bones. In this study, 
      we performed a detailed phenotypic analysis of BTC-tg mice at 3, 6, and 9 wk of 
      age. Osteoblastic cells from transgenic mice showed strong expression of BTC as 
      determined by Western blots and by immunohistochemistry on bone sections. In 
      femurs of male and female BTC-tg mice, we found reduced longitudinal bone growth 
      and a pronounced increase in total volumetric BMD. The increased femoral BMD was 
      mainly caused by augmented endocortical bone apposition and subsequent cortical 
      bone thickening. In contrast, vertebral BMD was reduced in BTC-tg mice of both 
      sexes. An overall similar phenotype was found in 6-mo-old BTC-tg mice. The 
      increase in cortical bone mass in the appendicular skeleton of BTC-tg mice was 
      largely blocked when they were crossed into the Egfr (Wa5) background 
      characterized by a dominant negative EGFR. Our study showed that overexpression 
      of BTC results in an EGFR-dependent upregulation of cortical bone mass in the 
      appendicular skeleton of mice, uncovering a potential novel anabolic pathway for 
      cortical bone.
FAU - Schneider, Marlon R
AU  - Schneider MR
AD  - Institute of Molecular Animal Breeding and Biotechnology, Gene Center, and 
      Department of Veterinary Sciences, LMU Munich, Munich, Germany. 
      schnder@lmb.uni-muenchen.de
FAU - Mayer-Roenne, Bettina
AU  - Mayer-Roenne B
FAU - Dahlhoff, Maik
AU  - Dahlhoff M
FAU - Proell, Verena
AU  - Proell V
FAU - Weber, Karin
AU  - Weber K
FAU - Wolf, Eckhard
AU  - Wolf E
FAU - Erben, Reinhold G
AU  - Erben RG
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
RN  - 0 (Betacellulin)
RN  - 0 (Biomarkers)
RN  - 0 (Btc protein, mouse)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Ligands)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Aging
MH  - Animals
MH  - Betacellulin
MH  - Biomarkers/metabolism
MH  - Bone Density
MH  - Bone and Bones/*pathology
MH  - Chickens
MH  - ErbB Receptors/*metabolism
MH  - Femur/physiology
MH  - Intercellular Signaling Peptides and Proteins/*metabolism
MH  - Ligands
MH  - Mice
MH  - Mice, Transgenic
MH  - Organ Size
MH  - Osteoblasts/metabolism
MH  - Phenotype
MH  - Spine/physiology
MH  - Transgenes
EDAT- 2008/12/04 09:00
MHDA- 2009/05/19 09:00
CRDT- 2008/12/04 09:00
PHST- 2008/12/04 09:00 [pubmed]
PHST- 2009/05/19 09:00 [medline]
PHST- 2008/12/04 09:00 [entrez]
AID - 10.1359/jbmr.081202 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2009 Mar;24(3):455-67. doi: 10.1359/jbmr.081202.