PMID- 22700586
OWN - NLM
STAT- MEDLINE
DCOM- 20121210
LR  - 20211021
IS  - 1944-9917 (Electronic)
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 26
IP  - 8
DP  - 2012 Aug
TI  - BDNF alters ERK/p38 MAPK activity ratios to promote differentiation in growth 
      plate chondrocytes.
PG  - 1406-16
LID - 10.1210/me.2012-1063 [doi]
AB  - The ERK and p38 MAPK pathways are well-known transducers of signals that regulate 
      proliferation and differentiation, but precisely how these pathways control 
      growth plate chondrocyte development is unclear. For example, the ERK pathway has 
      been reported to be required by some investigators but inhibitory to chondrocyte 
      development by others. Moreover, how these two pathways interact to regulate 
      chondrocyte development is even less clear. Using primary bovine growth plate 
      chondrocytes and murine ATDC5 cells, we demonstrate that the ERK and p38 pathways 
      have opposing effects on proliferation but are both absolutely required for 
      differentiation. Two factors that promote chondrocyte differentiation, 
      brain-derived neurotrophic factor (BDNF) and C-type natriuretic peptide, increase 
      p38 activity while decreasing, but not completely inhibiting, ERK activity. The 
      attenuation of ERK activity by BDNF occurs via p38-dependent raf-1 inhibition. 
      The inhibition of raf-1 by p38 is direct, because purified p38 protein inhibits 
      the kinase activity of purified active raf-1 as well as raf-1 immunoprecipitated 
      from chondrocyte lysates. Moreover, IGF-I, which stimulates proliferation, 
      suppresses p38 activation. This work describes a model wherein unopposed IGF-I 
      promotes high ERK/p38 activity ratios favoring proliferation, whereas BDNF 
      signals a transition to differentiation by decreasing the ERK/p38 activity ratio 
      without completely inhibiting ERK, which involves the direct inhibition of raf-1 
      by p38.
FAU - Hutchison, Michele R
AU  - Hutchison MR
AD  - Department of Pediatrics, University of Texas Southwestern Medical Center, 
      Dallas, Texas 75390-9063, USA. michele.hutchison@utsouthwestern.edu
LA  - eng
GR  - K08 DK073447/DK/NIDDK NIH HHS/United States
GR  - DK073447/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120614
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Insulin)
RN  - 127869-51-6 (Natriuretic Peptide, C-Type)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Cattle
MH  - *Cell Differentiation
MH  - Cells, Cultured
MH  - Chondrocytes/enzymology/metabolism/*physiology
MH  - Enzyme Activation
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Growth Plate/*cytology
MH  - Insulin/pharmacology/physiology
MH  - Insulin-Like Growth Factor I/physiology
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - MAP Kinase Signaling System
MH  - Male
MH  - Mice
MH  - Natriuretic Peptide, C-Type/physiology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-raf/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
PMC - PMC3404299
EDAT- 2012/06/16 06:00
MHDA- 2012/12/12 06:00
PMCR- 2013/08/01
CRDT- 2012/06/16 06:00
PHST- 2012/06/16 06:00 [entrez]
PHST- 2012/06/16 06:00 [pubmed]
PHST- 2012/12/12 06:00 [medline]
PHST- 2013/08/01 00:00 [pmc-release]
AID - me.2012-1063 [pii]
AID - ME-12-1063 [pii]
AID - 10.1210/me.2012-1063 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2012 Aug;26(8):1406-16. doi: 10.1210/me.2012-1063. Epub 2012 Jun 
      14.