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
- 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
-
Advances in Regulating Tumorigenicity and Metastasis of Cancer Through TrkB Signaling
Current Cancer Drug Targets The Functions of Histone Modification Enzymes in Cancer
Current Protein & Peptide Science VEGF/VEGFR Pathway Inhibitors as Anti-Angiogenic Agents: Present and Future
Current Cancer Drug Targets Tumor Bone Diseases: Molecular Mechanisms and Opportunities for Novel Treatments
Current Medicinal Chemistry - Anti-Cancer Agents Multifunctional Proteins in Tumorigenesis: Aminoacyl-tRNA Synthetases and Translational Components
Current Proteomics Association of GRP78, HIF-1α and BAG3 Expression with the Severity of Chronic Lymphocytic Leukemia
Anti-Cancer Agents in Medicinal Chemistry Mechanisms of Beneficial Effects of High Molecular Weight Hyaluronan on Cultured Cartilage Tissue
Current Rheumatology Reviews Antiproliferative Activity of Cobra Venom Cytotoxins
Current Topics in Medicinal Chemistry Image Guided Biopsy of Musculoskeletal Lesions with Low Diagnostic Yield
Current Medical Imaging Structural Basis and Therapeutic Implication of the Interaction of CCN Proteins with Glycoconjugates
Current Pharmaceutical Design Detection of Early Cancer: Genetics or Immunology? Serum Autoantibody Profiles as Markers of Malignancy
Anti-Cancer Agents in Medicinal Chemistry A Prognostic Nomogram for Predicting Overall Survival in Pediatric Wilms Tumor Based on an Autophagy-related Gene Signature
Combinatorial Chemistry & High Throughput Screening Designing Novel Therapies Against Sarcomas in the Era of Personalized Medicine and Economic Crisis
Current Pharmaceutical Design Monoclonal Antibody Therapies Targeting Pancreatic Ductal Adenocarcinoma
Current Drug Discovery Technologies Novel Benzo[B]Furans with Anti-Microtubule Activity Upregulate Expression of Apoptotic Genes and Arrest Leukemia Cells in G2/M Phase
Anti-Cancer Agents in Medicinal Chemistry Development of Novel Therapeutics Targeting Isocitrate Dehydrogenase Mutations in Cancer
Current Topics in Medicinal Chemistry Histone Deacetylase Inhibitors: Recent Insights from Basic to Clinical Knowledge & Patenting of Anti-Cancer Actions
Recent Patents on Anti-Cancer Drug Discovery Alginate Bead-Encapsulated PEDF Induces Ectopic Bone Formation In Vivo in the Absence of Co-Administered Mesenchymal Stem Cells
Current Drug Targets Withdrawal Notice: Drug Repurposing for Prospective Anti-Cancer Agents Along with the Clinical Status of the Repurposed Drug
Anti-Cancer Agents in Medicinal Chemistry Synthesis and Biological Evaluation of Some Hydrazone Derivatives as Anti-inflammatory Agents
Letters in Drug Design & Discovery