Mechanical Impact Induces Cartilage Degradation via Mitogen Activated Protein Kinases.
Summary of "Mechanical Impact Induces Cartilage Degradation via Mitogen Activated Protein Kinases."
OBJECTIVE:
To determine the activation of 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 loss were determined with fluorescent microscopy and 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 1hr post-impaction. At 24hr, enhanced phosphorylation of p38 and ERK1/2 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 proteoglycan losses. Quantative Real-time PCR analysis revealed that blunt impaction significantly up-regulated MMP-13, TNF-alpha, and ADAMTS-5 expression.
CONCLUSION:
These findings implicate p38 and ERK MAPKs in the post injury spread of cartilage degeneration and suggest that the risk of 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.
Affiliation
Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
Journal Details
This article was published in the following journal.
Name: Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society
ISSN: 1522-9653
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20813194
- DOI: http://dx.doi.org/10.1016/j.joca.2010.08.014
Medical and Biotech [MESH] Definitions
Ets-domain Protein Elk-1
A member of the ternary complex family of ets-related transcription factors that is regulated by MITOGEN-ACTIVATED PROTEIN KINASES including JNK MITOGEN-ACTIVATED PROTEIN KINASES; MITOGEN-ACTIVATED PROTEIN KINASE 1; MITOGEN-ACTIVATED PROTEIN KINASE 3; and P38 MITOGEN-ACTIVATED PROTEIN KINASES.
Map Kinase Kinase 3
A mitogen-activated protein kinase kinase with specificity for a subset of P38 MITOGEN-ACTIVATED PROTEIN KINASES that includes MITOGEN-ACTIVATED PROTEIN KINASE 12; MITOGEN-ACTIVATED PROTEIN KINASE 13; and MITOGEN-ACTIVATED PROTEIN KINASE 14.
Map Kinase Kinase 4
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.
Mitogen-activated Protein Kinases
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Map Kinase Kinase Kinases
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
PubMed Articles
Objectives. To determine the effects and mechanism of action of lithium chloride (LiCl) on cartilage destruction induced by the pro-inflammatory cytokines IL-1, IL-1 + oncostatin M and TNF-alpha. Meth...
CD44, an adhesion molecule, has been reported to be a binding site for Mycobacterium tuberculosis (M. tuberculosis) in macrophages and it also mediates mycobacterial phagocytosis, macrophage recruitme...
Mechanical Properties of Natural Cartilage and Tissue Engineered Constructs.
There has been much research over the past two decades with the aim of engineering cartilage constructs for repairing or restoring damaged cartilage. To engineer healthy neocartilage, the constructs m...
Quantitative measurement of articular cartilage using optical coherence tomography (OCT) is a potential approach for diagnosing the early degeneration of cartilage and assessing the quality of its rep...
Clinical Trials
Activated Protein C in Acute Stroke Trial
The purpose of this research study is to determine the safety and learn more about the dose of Activated Protein C (APC) in reducing the damage from stroke.
Efficacy and Safety of PG-530742 in the Treatment of Mild to Moderate Knee Osteoarthritis
Matrix metalloproteinases have been implicated in the cartilage degradation that occurs in osteoarthritis. PG-530742 inhibits some of these matrix metalloproteinases, thus potentially limi...
Knee Articular Cartilage Debridement in Conjunction With Partial Meniscectomy
The purpose of this post-marketing surveillance study is to determine the proportion of study participants who demonstrate tissue stability, as seen using magnetic resonance imaging (MRI),...
This will be a double-blind, placebo controlled cross-over study. After enrolment and initial assessments, subjects will receive oral SB681323 or matching placebo for 14 days. SB681323 wil...
The Cartilage Autograft Implantation System (CAIS) is designed as a single surgical treatment of damaged knee cartilage using the subject's own healthy cartilage obtained from a non-weight...
