PMID- 26103093
OWN - NLM
STAT- MEDLINE
DCOM- 20160825
LR  - 20220129
IS  - 1873-2763 (Electronic)
IS  - 1873-2763 (Linking)
VI  - 81
DP  - 2015 Dec
TI  - Osteoblast-specific overexpression of amphiregulin leads to transient increase in 
      femoral cancellous bone mass in mice.
PG  - 36-46
LID - S8756-3282(15)00248-3 [pii]
LID - 10.1016/j.bone.2015.06.012 [doi]
AB  - The epidermal growth factor receptor ligand amphiregulin (AREG) has been 
      implicated in bone physiology and in bone anabolism mediated by intermittent 
      parathyroid hormone treatment. However, the functions of AREG in bone have been 
      only incipiently evaluated in vivo. Here, we generated transgenic mice 
      overexpressing AREG specifically in osteoblasts (Col1-Areg). pQCT analysis of the 
      femoral metaphysis revealed increased trabecular bone mass at 4, 8, and 10weeks 
      of age in Col1-Areg mice compared to control littermates. However, the high bone 
      mass phenotype was transient and disappeared in older animals. Micro-CT analysis 
      of the secondary spongiosa confirmed increased trabecular bone volume and 
      trabecular number in the distal femur of 4-week-old AREG-tg mice compared to 
      control littermates. Furthermore, mu-CT analysis of the primary spongiosa revealed 
      unaltered production of new bone trabeculae in distal femora of Col1-Areg mice. 
      Histomorphometric analysis revealed a reduced number of osteoclasts in 4-week-old 
      Col1-Areg mice, but not at later time points. Cancellous bone formation rate 
      remained unchanged in Col1-Areg mice at all time points. In addition, bone mass 
      and bone turnover in lumbar vertebral bodies were similar in Col1-Areg and 
      control mice at all ages examined. Proliferation and differentiation of 
      osteoblasts isolated from neonatal calvariae did not differ between Col1-Areg and 
      control mice. Taken together, these data suggest that AREG overexpression in 
      osteoblasts induces a transient high bone mass phenotype in the trabecular 
      compartment of the appendicular skeleton by a growth-related, non-cell autonomous 
      mechanism, leading to a positive bone balance with unchanged bone formation and 
      lowered bone resorption.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Vaidya, Mithila
AU  - Vaidya M
AD  - Institute of Physiology, Pathophysiology and Biophysics, Department of Biomedical 
      Research, University of Veterinary Medicine Vienna, Veterinarplatz 1, Vienna 
      1210, Austria.
FAU - Lehner, Diana
AU  - Lehner D
AD  - Institute of Physiology, Pathophysiology and Biophysics, Department of Biomedical 
      Research, University of Veterinary Medicine Vienna, Veterinarplatz 1, Vienna 
      1210, Austria.
FAU - Handschuh, Stephan
AU  - Handschuh S
AD  - VetCore Facility for Research and Technology, University of Veterinary Medicine 
      Vienna, Veterinarplatz 1, Vienna 1210, Austria.
FAU - Jay, Freya F
AU  - Jay FF
AD  - Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU 
      Munich, Germany.
FAU - Erben, Reinhold G
AU  - Erben RG
AD  - Institute of Physiology, Pathophysiology and Biophysics, Department of Biomedical 
      Research, University of Veterinary Medicine Vienna, Veterinarplatz 1, Vienna 
      1210, Austria.
FAU - Schneider, Marlon R
AU  - Schneider MR
AD  - Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU 
      Munich, Germany. Electronic address: marlon.schneider@lmu.de.
LA  - eng
GR  - I 764/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150620
PL  - United States
TA  - Bone
JT  - Bone
JID - 8504048
RN  - 0 (Amphiregulin)
SB  - IM
MH  - Amphiregulin/*biosynthesis
MH  - Animals
MH  - Blotting, Northern
MH  - Bone Density/physiology
MH  - Bone Remodeling/*physiology
MH  - Femur/*diagnostic imaging/metabolism
MH  - Laser Capture Microdissection
MH  - Mice
MH  - Mice, Transgenic
MH  - Osteoblasts/*metabolism
MH  - Osteogenesis/*physiology
MH  - Real-Time Polymerase Chain Reaction
MH  - X-Ray Microtomography
OTO - NOTNLM
OT  - Amphiregulin
OT  - EGFR
OT  - Osteoblast
OT  - Osteoclast
OT  - Transgenic mice
EDAT- 2015/06/24 06:00
MHDA- 2016/08/26 06:00
CRDT- 2015/06/24 06:00
PHST- 2014/11/21 00:00 [received]
PHST- 2015/05/28 00:00 [revised]
PHST- 2015/06/17 00:00 [accepted]
PHST- 2015/06/24 06:00 [entrez]
PHST- 2015/06/24 06:00 [pubmed]
PHST- 2016/08/26 06:00 [medline]
AID - S8756-3282(15)00248-3 [pii]
AID - 10.1016/j.bone.2015.06.012 [doi]
PST - ppublish
SO  - Bone. 2015 Dec;81:36-46. doi: 10.1016/j.bone.2015.06.012. Epub 2015 Jun 20.