Mechanical impact induces cartilage degradation via mitogen activated protein kinases

Autor: N. J. Stroud, N. Nicholson, Lei Ding, Danping Guo, Emily Heying, Joseph A. Buckwalter, G. A. Homandberg, James A. Martin
Rok vydání: 2010
Předmět:
Cartilage
Articular
MAPK/ERK pathway
Cell Survival
Post-traumatic osteoarthritis
p38 mitogen-activated protein kinases
Immunoblotting
Biomedical Engineering
Polymerase Chain Reaction
p38 Mitogen-Activated Protein Kinases
Article
Chondrocyte
03 medical and health sciences
Chondrocytes
0302 clinical medicine
Rheumatology
Cartilage damage
medicine
Animals
Orthopedics and Sports Medicine
Extracellular Signal-Regulated MAP Kinases
Protein kinase A
030304 developmental biology
030203 arthritis & rheumatology
0303 health sciences
Cell Death
biology
Inhibitors
Kinase
Cartilage
Cell biology
Disease Models
Animal
Impact
MAP kinases
medicine.anatomical_structure
Biochemistry
Mitogen-activated protein kinase
biology.protein
Phosphorylation
Cattle
Proteoglycans
Stress
Mechanical
Mitogen-Activated Protein Kinases
Zdroj: Osteoarthritis and Cartilage. 18:1509-1517
ISSN: 1063-4584
DOI: 10.1016/j.joca.2010.08.014
Popis: Summary 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 20min 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)-α, 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-α.
Databáze: OpenAIRE
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