PMID- 26766111
OWN - NLM
STAT- MEDLINE
DCOM- 20171221
LR  - 20180829
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Linking)
VI  - 31
IP  - 6
DP  - 2016 Jun
TI  - Ameloblastin, an Extracellular Matrix Protein, Affects Long Bone Growth and 
      Mineralization.
PG  - 1235-46
LID - 10.1002/jbmr.2788 [doi]
AB  - Matrix molecules such as the enamel-related calcium-binding phosphoprotein 
      ameloblastin (AMBN) are expressed in multiple tissues, including teeth, bones, 
      and cartilage. Here we have asked whether AMBN is of functional importance for 
      timely long bone development and, if so, how it exerts its function related to 
      osteogenesis. Adolescent AMBN-deficient mice (AMBN(Delta5-6) ) suffered from a 33% to 
      38% reduction in femur length and an 8.4% shorter trunk spinal column when 
      compared with WT controls, whereas there was no difference between adult animals. 
      On a cellular level, AMBN truncation resulted in a shortened growth plate and a 
      41% to 49% reduction in the number of proliferating tibia chondrocytes and 
      osteoblasts. Bone marrow stromal cells (BMSCs) isolated from AMBN mutant mice 
      displayed defects in proliferation and differentiation potential as well as 
      cytoskeleton organization. Osteogenesis-related growth factors, such as 
      insulin-like growth factor 1 (IGF1) and BMP7, were also significantly (46% to 
      73%) reduced in AMBN-deficient BMSCs. Addition of exogenous AMBN restored 
      cytoskeleton structures in AMBN mutant BMSCs and resulted in a dramatic 400% to 
      600% increase in BMP2, BMP7, and Col1A expression. Block of RhoA diminished the 
      effect of AMBN on osteogenic growth factor and matrix protein gene expression. 
      Addition of exogenous BMP7 and IGF1 rescued the proliferation and differentiation 
      potential of AMBN-deficient BMSCs. Confirming the effects of AMBN on long bone 
      growth, back-crossing of mutant mice with full-length AMBN overexpressors 
      resulted in a complete rescue of AMBN(Delta5-6) bone defects. Together, these data 
      indicate that AMBN affects extracellular matrix production and cell adhesion 
      properties in the long bone growth plate, resulting in altered cytoskeletal 
      dynamics, increased osteogenesis-related gene expression, as well as osteoblast 
      and chondrocyte proliferation. We propose that AMBN facilitates rapid long bone 
      growth and an important growth spurt during the skeletogenesis of adolescent 
      tooth-bearing vertebrates. (c) 2016 American Society for Bone and Mineral Research.
CI  - (c) 2016 American Society for Bone and Mineral Research.
FAU - Lu, Xuanyu
AU  - Lu X
AD  - Department of Oral Biology, Brodie Laboratory for Craniofacial Genetics, 
      University of Illinois College of Dentistry, Chicago, IL, USA.
FAU - Fukumoto, Satoshi
AU  - Fukumoto S
AD  - Craniofacial Developmental Biology and Regeneration Branch, National Institute of 
      Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, 
      USA.
FAU - Yamada, Yoshihiko
AU  - Yamada Y
AD  - Craniofacial Developmental Biology and Regeneration Branch, National Institute of 
      Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, 
      USA.
FAU - Evans, Carla A
AU  - Evans CA
AD  - Department of Orthodontics, Brodie Laboratory for Craniofacial Genetics, 
      University of Illinois College of Dentistry, Chicago, IL, USA.
FAU - Diekwisch, Thomas Gh
AU  - Diekwisch TG
AD  - Department of Oral Biology, Brodie Laboratory for Craniofacial Genetics, 
      University of Illinois College of Dentistry, Chicago, IL, USA.
FAU - Luan, Xianghong
AU  - Luan X
AD  - Department of Oral Biology, Brodie Laboratory for Craniofacial Genetics, 
      University of Illinois College of Dentistry, Chicago, IL, USA.
AD  - Department of Orthodontics, Brodie Laboratory for Craniofacial Genetics, 
      University of Illinois College of Dentistry, Chicago, IL, USA.
LA  - eng
GR  - R01 DE019155/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160226
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 (Ambn protein, mouse)
RN  - 0 (Bone Morphogenetic Protein 7)
RN  - 0 (Dental Enamel Proteins)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (bmp7 protein, mouse)
RN  - 0 (insulin-like growth factor-1, mouse)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Animals
MH  - Bone Density/*physiology
MH  - Bone Morphogenetic Protein 7/genetics/metabolism
MH  - Dental Enamel Proteins/genetics/*metabolism
MH  - Extracellular Matrix Proteins/genetics/*metabolism
MH  - Femur/*growth & development
MH  - Insulin-Like Growth Factor I/genetics/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Osteogenesis/*physiology
OTO - NOTNLM
OT  - AMELOBLASTIN
OT  - BMP7
OT  - BONE DEVELOPMENT
OT  - IGF1
OT  - MESENCHYMAL CELLS
EDAT- 2016/01/15 06:00
MHDA- 2017/12/22 06:00
CRDT- 2016/01/15 06:00
PHST- 2015/08/27 00:00 [received]
PHST- 2016/01/06 00:00 [revised]
PHST- 2016/01/08 00:00 [accepted]
PHST- 2016/01/15 06:00 [entrez]
PHST- 2016/01/15 06:00 [pubmed]
PHST- 2017/12/22 06:00 [medline]
AID - 10.1002/jbmr.2788 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2016 Jun;31(6):1235-46. doi: 10.1002/jbmr.2788. Epub 2016 Feb 
      26.