PMID- 25538250
OWN - NLM
STAT- MEDLINE
DCOM- 20150508
LR  - 20240512
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 290
IP  - 7
DP  - 2015 Feb 13
TI  - Osteoblast menin regulates bone mass in vivo.
PG  - 3910-24
LID - 10.1074/jbc.M114.629899 [doi]
AB  - Menin, the product of the multiple endocrine neoplasia type 1 (Men1) tumor 
      suppressor gene, mediates the cell proliferation and differentiation actions of 
      transforming growth factor-beta (TGF-beta) ligand family members. In vitro, menin 
      modulates osteoblastogenesis and osteoblast differentiation promoted and 
      sustained by bone morphogenetic protein-2 (BMP-2) and TGF-beta, respectively. To 
      examine the in vivo function of menin in bone, we conditionally inactivated Men1 
      in mature osteoblasts by crossing osteocalcin (OC)-Cre mice with floxed Men1 
      (Men1(f/f)) mice to generate mice lacking menin in differentiating osteoblasts 
      (OC-Cre;Men1(f/f) mice). These mice displayed significant reduction in bone 
      mineral density, trabecular bone volume, and cortical bone thickness compared 
      with control littermates. Osteoblast and osteoclast number as well as mineral 
      apposition rate were significantly reduced, whereas osteocyte number was 
      increased. Primary calvarial osteoblasts proliferated more quickly but had 
      deficient mineral apposition and alkaline phosphatase activity. Although the mRNA 
      expression of osteoblast marker and cyclin-dependent kinase inhibitor genes were 
      all reduced, that of cyclin-dependent kinase, osteocyte marker, and pro-apoptotic 
      genes were increased in isolated Men1 knock-out osteoblasts compared with 
      controls. In contrast to the knock-out mice, transgenic mice overexpressing a 
      human menin cDNA in osteoblasts driven by the 2.3-kb Col1a1 promoter, showed a 
      gain of bone mass relative to control littermates. Osteoblast number and mineral 
      apposition rate were significantly increased in the Col1a1-Menin-Tg mice. 
      Therefore, osteoblast menin plays a key role in bone development, remodeling, and 
      maintenance.
CI  - (c) 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Kanazawa, Ippei
AU  - Kanazawa I
AD  - From the Departments of Medicine.
FAU - Canaff, Lucie
AU  - Canaff L
AD  - From the Departments of Medicine.
FAU - Abi Rafeh, Jad
AU  - Abi Rafeh J
AD  - Physiology.
FAU - Angrula, Aarti
AU  - Angrula A
AD  - From the Departments of Medicine.
FAU - Li, Jingjing
AU  - Li J
AD  - Dentistry.
FAU - Riddle, Ryan C
AU  - Riddle RC
AD  - Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, 
      Baltimore, Maryland 21205, and the Veterans Administration Medical Center, 
      Baltimore, Maryland 21201.
FAU - Boraschi-Diaz, Iris
AU  - Boraschi-Diaz I
AD  - Dentistry.
FAU - Komarova, Svetlana V
AU  - Komarova SV
AD  - Dentistry.
FAU - Clemens, Thomas L
AU  - Clemens TL
AD  - Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, 
      Baltimore, Maryland 21205, and the Veterans Administration Medical Center, 
      Baltimore, Maryland 21201.
FAU - Murshed, Monzur
AU  - Murshed M
AD  - From the Departments of Medicine, Dentistry.
FAU - Hendy, Geoffrey N
AU  - Hendy GN
AD  - From the Departments of Medicine, Physiology, Human Genetics, and Calcium 
      Research Laboratory, and Hormones and Cancer Research Unit, Royal Victoria 
      Hospital, McGill University, Montreal, Quebec H3A 1A1, Canada, 
      geoffrey.hendy@mcgill.ca.
LA  - eng
GR  - 123310/Canadian Institutes of Health Research/Canada
GR  - 776403/Canadian Institutes of Health Research/Canada
GR  - MOP-9315/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141223
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Blotting, Western
MH  - Bone Density
MH  - Bone Development/*physiology
MH  - Bone Morphogenetic Protein 2/genetics/metabolism
MH  - Bone and Bones/*physiology
MH  - *Cell Differentiation
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Female
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Multiple Endocrine Neoplasia Type 1/metabolism
MH  - Osteoblasts/*cytology/metabolism
MH  - Proto-Oncogene Proteins/*physiology
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Transforming Growth Factor beta/genetics/metabolism
PMC - PMC4326801
OTO - NOTNLM
OT  - Bone
OT  - Bone Morphogenetic Protein (BMP)
OT  - Gene Knockout
OT  - Menin
OT  - Mouse
OT  - Osteoblast
OT  - Osteoclast
OT  - Osteocyte
OT  - Transforming Growth Factor beta (TGF-B)
EDAT- 2014/12/30 06:00
MHDA- 2015/05/09 06:00
PMCR- 2016/02/13
CRDT- 2014/12/25 06:00
PHST- 2014/12/25 06:00 [entrez]
PHST- 2014/12/30 06:00 [pubmed]
PHST- 2015/05/09 06:00 [medline]
PHST- 2016/02/13 00:00 [pmc-release]
AID - S0021-9258(19)46981-0 [pii]
AID - M114.629899 [pii]
AID - 10.1074/jbc.M114.629899 [doi]
PST - ppublish
SO  - J Biol Chem. 2015 Feb 13;290(7):3910-24. doi: 10.1074/jbc.M114.629899. Epub 2014 
      Dec 23.