Journal article
Mechanical Impact Induces Cartilage Degradation via Mitogen Activated Protein Kinases
Osteoarthritis and cartilage, Vol.18(11), pp.1509-1517
11/2010
DOI: 10.1016/j.joca.2010.08.014
PMCID: PMC3013628
PMID: 20813194
Abstract
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)-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.
Details
- Title: Subtitle
- Mechanical Impact Induces Cartilage Degradation via Mitogen Activated Protein Kinases
- Creators
- Lei Ding - Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USAEmily Heying - Department of Biology, Wartburg College, Waverly, Iowa, USANathan Nicholson - Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USANicolas J Stroud - Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, USAGene A Homandberg - Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, North Dakota, USADanping Guo - Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, North Dakota, USAJoseph A Buckwalter - Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USAJames A Martin - Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Osteoarthritis and cartilage, Vol.18(11), pp.1509-1517
- DOI
- 10.1016/j.joca.2010.08.014
- PMID
- 20813194
- PMCID
- PMC3013628
- NLM abbreviation
- Osteoarthritis Cartilage
- ISSN
- 1063-4584
- eISSN
- 1522-9653
- Language
- English
- Date published
- 11/2010
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Injury Prevention Research Center
- Record Identifier
- 9984040014402771
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