Abstract
Osteoarthritis is characterised by degeneration of articular cartilage. It is thought to be primarily a disease of cartilage. Inflammatory response genes, such as proteinases, cyclooxygenase, and cytokines are implicated in its pathogenesis. The evidence for expression of these genes in articular cartilage in osteoarthritis is reviewed. The expression of inflammatory response genes is controlled by four major intracellular signalling pathways. These lead to activation of the three mitogen-activated protein kinases (MAPK) and the transcriptional regulator nuclear factor kappa (NFκ )-B. The current state of knowledge of the structure of these pathways is summarized. Pharmacological inhibitors of the protein kinases of the pathways in current use are described, and insights into chondrocyte gene expression obtained with them are discussed. Very limited use of these inhibitors has yet been made in animal models of osteoarthritis. The main use of the inhibitors in the near future will be in investigation of pathogenetic mechanisms in osteoarthritis, both in experimental animals and in vitro, with a view to identifying therapeutic targets. Prospects for using signalling pathway inhibitors for therapy in osteoarthritis are distant.
Keywords: Chondrocyte, MAP kinase, NF-κ B, matrix metalloproteinase, protein kinase, protein kinase inhibitor, inflammatory response, osteoarthritis
Current Drug Targets
Title: Inflammatory Signaling in Cartilage: MAPK and NF-κ B Pathways in Chondrocytes and the Use of Inhibitors for Research into Pathogenesis and Therapy of Osteoarthritis
Volume: 8 Issue: 2
Author(s): Jeremy Saklatvala
Affiliation:
Keywords: Chondrocyte, MAP kinase, NF-κ B, matrix metalloproteinase, protein kinase, protein kinase inhibitor, inflammatory response, osteoarthritis
Abstract: Osteoarthritis is characterised by degeneration of articular cartilage. It is thought to be primarily a disease of cartilage. Inflammatory response genes, such as proteinases, cyclooxygenase, and cytokines are implicated in its pathogenesis. The evidence for expression of these genes in articular cartilage in osteoarthritis is reviewed. The expression of inflammatory response genes is controlled by four major intracellular signalling pathways. These lead to activation of the three mitogen-activated protein kinases (MAPK) and the transcriptional regulator nuclear factor kappa (NFκ )-B. The current state of knowledge of the structure of these pathways is summarized. Pharmacological inhibitors of the protein kinases of the pathways in current use are described, and insights into chondrocyte gene expression obtained with them are discussed. Very limited use of these inhibitors has yet been made in animal models of osteoarthritis. The main use of the inhibitors in the near future will be in investigation of pathogenetic mechanisms in osteoarthritis, both in experimental animals and in vitro, with a view to identifying therapeutic targets. Prospects for using signalling pathway inhibitors for therapy in osteoarthritis are distant.
Export Options
About this article
Cite this article as:
Saklatvala Jeremy, Inflammatory Signaling in Cartilage: MAPK and NF-κ B Pathways in Chondrocytes and the Use of Inhibitors for Research into Pathogenesis and Therapy of Osteoarthritis, Current Drug Targets 2007; 8 (2) . https://dx.doi.org/10.2174/138945007779940115
DOI https://dx.doi.org/10.2174/138945007779940115 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
RNA Molecules in the Treatment of Human Diseases
Messenger and non-coding RNAs, including long and small transcripts, are mediators of gene expression. Gene expression at the RNA level shows significant aberrations in human diseases, including cancer, leukemia, lymphoma, cardiovascular diseases, and neurological disorders. Human transcripts serve either as biomarkers of diagnosis, prognosis, prediction of treatment response and/or therapy ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Computational Approaches for Translational Oncology: Concepts and Patents
Recent Patents on Anti-Cancer Drug Discovery Ewing’s Sarcoma Cancer Stem Cell Targeted Therapy
Current Stem Cell Research & Therapy Primary Tumors of the Sacrum: Imaging Findings
Current Medical Imaging The Evolving Landscape in the Development of Isocitrate Dehydrogenase Mutant Inhibitors
Mini-Reviews in Medicinal Chemistry Recent Advances and Strategies in Tumor Vasculature Targeted Nano-Drug Delivery Systems
Current Pharmaceutical Design Therapeutic Approach of Primary Bone Tumours by Bisphosphonates
Current Pharmaceutical Design Tumor Stroma Manipulation By MSC
Current Drug Targets One Hundred Faces of Cyclopamine
Current Pharmaceutical Design Regulation of Autophagy by Sphingolipids
Anti-Cancer Agents in Medicinal Chemistry The Role of Cellular Plasticity in Cancer Development
Current Medicinal Chemistry Malignant Mesothelioma Resistance to Apoptosis: Recent Discoveries and their Implication for Effective Therapeutic Strategies
Current Medicinal Chemistry Berberine Exerts Anti-cancer Activity by Modulating Adenosine Monophosphate- Activated Protein Kinase (AMPK) and the Phosphatidylinositol 3-Kinase/ Protein Kinase B (PI3K/AKT) Signaling Pathways
Current Pharmaceutical Design MiRNA153 Reduces Effects of Chemotherapeutic Agents or Small Molecular Kinase Inhibitor in HCC Cells
Current Cancer Drug Targets Targeting Matrix Metalloproteinases in Inflammatory Conditions
Current Drug Targets Intraarticular Treatments for Osteoarthritis: New Perspectives
Current Drug Targets Enhanced Free Radical Status of Cancer Cells Success and Failure of Prooxidant/Antioxidant Treatment
Current Signal Transduction Therapy Structural Basis and Therapeutic Implication of the Interaction of CCN Proteins with Glycoconjugates
Current Pharmaceutical Design Cancer Drug Discovery Targeting Histone Methyltransferases: An Update
Current Medicinal Chemistry Prepontine Chordoma Presenting with MRI Features of an Epidermoid Cyst: Case Presentation and a Mini-Review
Current Medical Imaging The Association of Collagenase with Human Diseases and its Therapeutic Potential in Overcoming them
Current Biotechnology