PMID- 18265001
OWN - NLM
STAT- MEDLINE
DCOM- 20080611
LR  - 20211203
IS  - 1058-8388 (Print)
IS  - 1097-0177 (Electronic)
IS  - 1058-8388 (Linking)
VI  - 237
IP  - 3
DP  - 2008 Mar
TI  - mTOR signaling contributes to chondrocyte differentiation.
PG  - 702-12
LID - 10.1002/dvdy.21464 [doi]
AB  - The mammalian Target Of Rapamycin (mTOR) is a nutrient-sensing protein kinase 
      that regulates numerous cellular processes. Fetal rat metatarsal explants were 
      used as a physiological model to study the effect of mTOR inhibition on 
      chondrogenesis. Insulin significantly enhanced their growth. Rapamycin 
      significantly diminished this response to insulin through a selective effect on 
      the hypertrophic zone. Cell proliferation (bromodeoxyuridine incorporation) was 
      unaffected by rapamycin. Similar observations were made when rapamycin was 
      injected to embryonic day (E) 19 fetal rats in situ. In the ATDC5 chondrogenic 
      cell line, rapamycin inhibited proteoglycan accumulation and collagen X 
      expression. Rapamycin decreased content of Indian Hedgehog (Ihh), a regulator of 
      chondrocyte differentiation. Addition of Ihh to culture medium reversed the 
      effect of rapamycin. We conclude that modulation of mTOR signaling contributes to 
      chondrocyte differentiation, perhaps through its ability to regulate Ihh. Our 
      findings support the hypothesis that nutrients, acting through mTOR, directly 
      influence chondrocyte differentiation and long bone growth.
CI  - (c) 2008 Wiley-Liss, Inc.
FAU - Phornphutkul, Chanika
AU  - Phornphutkul C
AD  - Department of Pediatrics, Division of Pediatric Endocrinology and Metabolism, 
      Rhode Island Hospital and Brown University, Providence, Rhode Island 02903, USA. 
      chanika_phornphutkul@brown.edu
FAU - Wu, Ke-Ying
AU  - Wu KY
FAU - Auyeung, Valerie
AU  - Auyeung V
FAU - Chen, Qian
AU  - Chen Q
FAU - Gruppuso, Philip A
AU  - Gruppuso PA
LA  - eng
GR  - R29 AG014399-06/AG/NIA NIH HHS/United States
GR  - HD35831/HD/NICHD NIH HHS/United States
GR  - R01 HD024455-19/HD/NICHD NIH HHS/United States
GR  - P20 GM104937/GM/NIGMS NIH HHS/United States
GR  - P20 RR024484/RR/NCRR NIH HHS/United States
GR  - P20RR024484/RR/NCRR NIH HHS/United States
GR  - R01 AG017021/AG/NIA NIH HHS/United States
GR  - R01 AG017021-08/AG/NIA NIH HHS/United States
GR  - R01 HD024455/HD/NICHD NIH HHS/United States
GR  - R01 HD035831-09/HD/NICHD NIH HHS/United States
GR  - R29 AG014399/AG/NIA NIH HHS/United States
GR  - R01 HD035831/HD/NICHD NIH HHS/United States
GR  - HD24455/HD/NICHD NIH HHS/United States
GR  - AG014399/AG/NIA NIH HHS/United States
GR  - AG017021/AG/NIA NIH HHS/United States
GR  - R01 AG014399/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Dev Dyn
JT  - Developmental dynamics : an official publication of the American Association of 
      Anatomists
JID - 9201927
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Insulin)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Bone Development
MH  - Bone and Bones/embryology
MH  - Cell Differentiation/drug effects
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Chondrocytes/cytology/*metabolism
MH  - *Chondrogenesis/drug effects
MH  - Growth Plate/*embryology/metabolism
MH  - Hedgehog Proteins/*metabolism
MH  - Insulin/metabolism
MH  - Organ Culture Techniques
MH  - Protein Kinases/*metabolism
MH  - Rats
MH  - Signal Transduction
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
PMC - PMC2768549
MID - NIHMS107016
EDAT- 2008/02/12 09:00
MHDA- 2008/06/12 09:00
PMCR- 2009/10/27
CRDT- 2008/02/12 09:00
PHST- 2008/02/12 09:00 [pubmed]
PHST- 2008/06/12 09:00 [medline]
PHST- 2008/02/12 09:00 [entrez]
PHST- 2009/10/27 00:00 [pmc-release]
AID - 10.1002/dvdy.21464 [doi]
PST - ppublish
SO  - Dev Dyn. 2008 Mar;237(3):702-12. doi: 10.1002/dvdy.21464.