PMID- 23661628
OWN - NLM
STAT- MEDLINE
DCOM- 20140813
LR  - 20211203
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Linking)
VI  - 28
IP  - 11
DP  - 2013 Nov
TI  - Metabolic regulation of osteoclast differentiation and function.
PG  - 2392-9
LID - 10.1002/jbmr.1976 [doi]
AB  - The osteoclast is a giant cell that resorbs calcified matrix by secreting acids 
      and collagenolytic enzymes. The molecular mechanisms underlying metabolic 
      adaptation to the increased biomass and energetic demands of osteoclastic bone 
      resorption remain elusive. Here we show that during osteoclastogenesis the 
      expression of both glucose transporter 1 (Glut1) and glycolytic genes is 
      increased, whereas the knockdown of hypoxia-inducible factor 1-alpha (Hif1alpha), as 
      well as glucose deprivation, inhibits the bone-resorbing function of osteoclasts, 
      along with a suppression of Glut1 and glycolytic gene expression. Furthermore, 
      the expression of the glutamine transporter solute carrier family 1 (neutral 
      amino acid transporter), member 5 (Slc1a5) and glutaminase 1 was increased early 
      in differentiation, and a depletion of L-glutamine or pharmacological inhibition 
      of the Slc1a5 transporter suppressed osteoclast differentiation and function. 
      Inhibition of c-Myc function abrogated osteoclast differentiation and function, 
      along with a suppression of Slc1a5 and glutaminase 1 gene expression. Genetic and 
      pharmacological inhibition of mammalian target of rapamycin (mTOR), as well as 
      the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), 
      inhibited osteoclastogenesis. Thus, the uptake of glucose and glutamine and 
      utilization of the carbon sources derived from them, coordinated by HIF1alpha and 
      c-Myc, are essential for osteoclast development and bone-resorbing activity 
      through a balanced regulation of the nutrient and energy sensors, mTOR and AMPK.
CI  - (c) 2013 American Society for Bone and Mineral Research.
FAU - Indo, Yoriko
AU  - Indo Y
AD  - Department of Bone and Joint Disease, National Center for Geriatrics and 
      Gerontology, Obu, Aichi, Japan.
FAU - Takeshita, Sunao
AU  - Takeshita S
FAU - Ishii, Kiyo-Aki
AU  - Ishii KA
FAU - Hoshii, Takayuki
AU  - Hoshii T
FAU - Aburatani, Hiroyuki
AU  - Aburatani H
FAU - Hirao, Atsushi
AU  - Hirao A
FAU - Ikeda, Kyoji
AU  - Ikeda K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
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 (Amino Acid Transport System ASC)
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (Slc1a5 protein, mouse)
RN  - 0 (Slc2a1 protein, mouse)
RN  - 0RH81L854J (Glutamine)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Amino Acid Transport System ASC/metabolism
MH  - Animals
MH  - Bone Resorption/enzymology/genetics/pathology
MH  - *Cell Differentiation/drug effects/genetics
MH  - Gene Expression Regulation/drug effects
MH  - Glucose/metabolism
MH  - Glucose Transporter Type 1/genetics/metabolism
MH  - Glutamine/pharmacology
MH  - Glycolysis/drug effects
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Minor Histocompatibility Antigens
MH  - Osteoclasts/drug effects/*metabolism/*pathology
MH  - Osteogenesis/drug effects/genetics
MH  - Proto-Oncogene Proteins c-myc/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - BIOENERGETICS
OT  - BIOSYNTHESIS
OT  - GLUTAMINOLYSIS
OT  - GLYCOLYSIS
OT  - OSTEOCLAST
EDAT- 2013/05/11 06:00
MHDA- 2014/08/15 06:00
CRDT- 2013/05/11 06:00
PHST- 2013/03/10 00:00 [received]
PHST- 2013/04/16 00:00 [revised]
PHST- 2013/04/24 00:00 [accepted]
PHST- 2013/05/11 06:00 [entrez]
PHST- 2013/05/11 06:00 [pubmed]
PHST- 2014/08/15 06:00 [medline]
AID - 10.1002/jbmr.1976 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2013 Nov;28(11):2392-9. doi: 10.1002/jbmr.1976.