PMID- 20813194
OWN - NLM
STAT- MEDLINE
DCOM- 20110224
LR  - 20220330
IS  - 1522-9653 (Electronic)
IS  - 1063-4584 (Print)
IS  - 1063-4584 (Linking)
VI  - 18
IP  - 11
DP  - 2010 Nov
TI  - Mechanical impact induces cartilage degradation via mitogen activated protein 
      kinases.
PG  - 1509-17
LID - 10.1016/j.joca.2010.08.014 [doi]
AB  - OBJECTIVE: To determine the activation of Mitogen activated protein (MAP) kinases 
      in and around cartilage subjected to mechanical damage and to determine the 
      effects of their inhibitors on impaction-induced chondrocyte death and cartilage 
      degeneration. DESIGN: The phosphorylation of MAP kinases was examined with 
      confocal microscopy and immunoblotting. The effects of MAP kinase inhibitors on 
      impaction-induced chondrocyte death and proteoglycan (PG) loss were determined 
      with fluorescent microscopy and 1, 9-Dimethyl-Methylene Blue (DMMB) assay. The 
      expression of catabolic genes at mRNA levels was examined with quantitative 
      real-time PCR. RESULTS: Early p38 activation was detected at 20 min and 1h 
      post-impaction. At 24h, enhanced phosphorylation of p38 and extracellular 
      signal-regulated protein kinase (ERK)1/2 was visualized in chondrocytes from in 
      and around impact sites. The phosphorylation of p38 was increased by 3.0-fold in 
      impact sites and 3.3-fold in adjacent cartilage. The phosphorylation of ERK-1 was 
      increased by 5.8-fold in impact zone and 5.4-fold in adjacent cartilage; the 
      phosphorylation of ERK-2 increased by 4.0-fold in impacted zone and 3.6-fold in 
      adjacent cartilage. Furthermore, the blocking of p38 pathway did not inhibit 
      impaction-induced ERK activation. The inhibition of p38 or ERK pathway 
      significantly reduced injury-related chondrocyte death and PG losses. 
      Quantitative Real-time PCR analysis revealed that blunt impaction significantly 
      up-regulated matrix metalloproteinase (MMP)-13, Tumor necrosis factor (TNF)-alpha, 
      and ADAMTS-5 expression. CONCLUSION: These findings implicate p38 and ERK mitogen 
      activated protein kinases (MAPKs) in the post-injury spread of cartilage 
      degeneration and suggest that the risk of post-traumatic osteoarthritis (PTOA) 
      following joint trauma could be decreased by blocking their activities, which 
      might be involved in up-regulating expressions of MMP-13, ADAMTS-5, and TNF-alpha.
CI  - Copyright (c) 2010 Osteoarthritis Research Society International. Published by 
      Elsevier Ltd. All rights reserved.
FAU - Ding, L
AU  - Ding L
AD  - Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and 
      Clinics, Iowa City, Iowa 52242, USA.
FAU - Heying, E
AU  - Heying E
FAU - Nicholson, N
AU  - Nicholson N
FAU - Stroud, N J
AU  - Stroud NJ
FAU - Homandberg, G A
AU  - Homandberg GA
FAU - Buckwalter, J A
AU  - Buckwalter JA
FAU - Guo, D
AU  - Guo D
FAU - Martin, J A
AU  - Martin JA
LA  - eng
GR  - P50 AR055533/AR/NIAMS NIH HHS/United States
GR  - S10 RR025439/RR/NCRR NIH HHS/United States
GR  - 1 P50 AR055533/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20100909
PL  - England
TA  - Osteoarthritis Cartilage
JT  - Osteoarthritis and cartilage
JID - 9305697
RN  - 0 (Proteoglycans)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Cartilage, Articular/enzymology/*injuries/*metabolism
MH  - Cattle
MH  - Cell Death/drug effects/physiology
MH  - Cell Survival/physiology
MH  - Chondrocytes/enzymology/physiology
MH  - Disease Models, Animal
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Immunoblotting
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Polymerase Chain Reaction
MH  - Proteoglycans/analysis
MH  - Stress, Mechanical
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC3013628
MID - NIHMS238580
COIS- COMPETING INTERESTS The authors have no financial or personal relationships with 
      entities that could have influenced this work.
EDAT- 2010/09/04 06:00
MHDA- 2011/02/25 06:00
PMCR- 2011/11/01
CRDT- 2010/09/04 06:00
PHST- 2009/12/08 00:00 [received]
PHST- 2010/08/17 00:00 [revised]
PHST- 2010/08/19 00:00 [accepted]
PHST- 2010/09/04 06:00 [entrez]
PHST- 2010/09/04 06:00 [pubmed]
PHST- 2011/02/25 06:00 [medline]
PHST- 2011/11/01 00:00 [pmc-release]
AID - S1063-4584(10)00291-8 [pii]
AID - 10.1016/j.joca.2010.08.014 [doi]
PST - ppublish
SO  - Osteoarthritis Cartilage. 2010 Nov;18(11):1509-17. doi: 
      10.1016/j.joca.2010.08.014. Epub 2010 Sep 9.