Artrose - kraakbeen regeneratie en pijnbestrijding
Let op: OA = Osteoarthritis = ArtrosePathology Osteoarthritis
- Medical management of osteoarthritis of the knee and hip joints
Osteoarthritis (OA) is a chronic, degenerative disorder of multifactorial aetiology, characterised by loss of articular cartilage and periarticular bone remodelling. OA causes joint pain, typically worse with weight bearing and activity, and stiffness after inactivity. There is no cure, and gradual, although slow, progression is most common. Almost 1.2 million Australians have symptoms of OA, and 13% are classified as disabled or handicapped. As well as affecting over half of people aged over 75 years, OA is a significant problem for 10% of adults still in the workforce. Overall, OA is the leading cause of musculoskeletal pain, disability and handicap in Australia. Goals of managing OA include controlling pain, maintaining and improving the range of movement and stability of affected joints, and limiting functional impairment. These goals should be achieved with minimal toxicity. Joint arthroplasty is indicated by end-stage joint failure with intractable pain, but most patients will be managed without surgery. Management must be individualised and patient-centred, and usually involves multiple strategies. Most morbidity is associated with OA of the large weight-bearing joints (the knee and hip). Here, we provide a pragmatic outline of the medical management of OA of these joints. - The pathophysiology of osteoarthritis
Osteoarthritis (OA) is a complex disease whose pathogenesis includes the contribution of biomechanical and metabolic factors which, altering the tissue homeostasis of articular cartilage and subchondral bone, determine the predominance of destructive over productive processes. A key role in the pathophysiology of articular cartilage is played by cell/extra-cellular matrix (ECM) interactions, which are mediated by cell surface integrins. In a physiologic setting, integrins modulate cell/ECM signaling, essential for regulating growth and differentiation and maintaining cartilage homeostasis. During OA, abnormal integrin expression alters cell/ECM signaling and modifies chondrocyte synthesis, with the following imbalance of destructive cytokines over regulatory factors. IL-1, TNF-alpha and other pro-catabolic cytokines activate the enzymatic degradation of cartilage matrix and are not counterbalanced by adequate synthesis of inhibitors. The main enzymes involved in ECM breakdown are metalloproteinases (MMPs), which are sequentially activated by an amplifying cascade. MMP activity is partially inhibited by the tissue inhibitors of MMPs (TIMPs), whose synthesis is low compared with MMP production in OA cartilage. Intriguing is the role of growth factors such as TGF-beta, IFG, BMP, NGF, and others, which do not simply repair the tissue damage induced by catabolic factors, but play an important role in OA pathogenesis. - The role Protein kinase Czeta is up-regulated in osteoarthritic cartilage and is required for activation of NF-kappaB by tumor necrosis factor and interleukin-1 in articular chondrocytes
Protein kinase Czeta (PKCzeta) is an intracellular serine/threonine protein kinase that has been implicated in the signaling pathways for certain inflammatory cytokines, including interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha), in some cell types. A study of gene expression in articular chondrocytes from osteoarthritis (OA) patients revealed that PKCzeta is transcriptionally up-regulated in human OA articular cartilage clinical samples. This finding led to the hypothesis that PKCzeta may be an important signaling component of cytokine-mediated cartilage matrix destruction in articular chondrocytes, believed to be an underlying factor in the pathophysiology of OA. IL-1 treatment of chondrocytes in culture resulted in rapidly increased phosphorylation of PKCzeta, implicating PKCzeta activation in the signaling pathway. Chondrocyte cell-based assays were used to evaluate the contribution of PKCzeta activity in NF-kappaB activation and extracellular matrix degradation mediated by IL-1, TNF, or sphingomyelinase. In primary chondrocytes, IL-1 and TNF-alpha caused an increase in NF-kappaB activity resulting in induction of aggrecanase-1 and aggrecanase-2 expression, with consequent increased proteoglycan degradation. This effect was blocked by the pan-specific PKC inhibitors RO 31-8220 and bisindolylmaleimide I, partially blocked by Gö 6976, and was unaffected by the PKCzeta-sparing inhibitor calphostin C. A cell-permeable PKCzeta pseudosubstrate peptide inhibitor was capable of blocking TNFand IL-1-mediated NF-kappaB activation and proteoglycan degradation in chondrocyte pellet cultures. In addition, overexpression of a dominant negative PKCzeta protein effectively prevented cytokine-mediated NF-kappaB activation in primary chondrocytes. These data implicate PKCzeta as a necessary component of the IL-1 and TNF signaling pathways in chondrocytes that result in catabolic destruction of extracellular matrix proteins in osteoarthritic cartilage. - Protein kinase Czeta is up-regulated in osteoarthritic cartilage and is required for activation of NF-kappaB by tumor necrosis factor and interleukin-1 in articular chondrocytes
In summary, modulation of cytokines that control MMP gene up-regulation would appear to be fertile targets for drug development in the treatment of OA. Several studies illustrate the potential importance of modulating IL-1 activity as a means to reduce the progression of the structural changes in OA. In the experimental dog and rabbit models of OA, we have demonstrated that in vivo intraarticular injections of the IL-Ra gene can prevent the progression of structural changes in OA. Future directions in the research and treatment of osteoarthritis (OA) will be based on the emerging picture of pathophysiological events that modulate the initiation and progression of OA. - The contribution of adipose tissue and adipokines to inflammation in joint disease
Adipokines are proteins produced by white adipose tissue, which is an active secretory organ. Regulation of immune and inflammatory responses is among the multiple physiological processes involving adipokines. Leptin, adiponectin and resistin are the most extensively studied adipokines. Leptin may promote inflammation by inducing Th1 phenotype development, whereas adiponectin may combat inflammation by reducing the production of pro-inflammatory cytokines. Resistin belongs to a family of proteins found in foci of inflammation, where they contribute to the inflammatory response. All three adipokines have been detected in synovial fluid from joints affected with the inflammatory disease rheumatoid arthritis (RA) or the degenerative disease osteoarthritis (OA). Recent evidence points to involvement of leptin in RA and OA and indicates that adiponectin and/or resistin mediate inflammation in arthritis. Thus, fat tissue is an active organ whose products contribute to inflammatory and degenerative processes underlying common joint diseases. - Adipose tissue, adipokines, and inflammation
White adipose tissue is no longer considered an inert tissue mainly devoted to energy storage but is emerging as an active participant in regulating physiologic and pathologic processes, including immunity and inflammation. Macrophages are components of adipose tissue and actively participate in its activities. Furthermore, cross-talk between lymphocytes and adipocytes can lead to immune regulation. Adipose tissue produces and releases a variety of proinflammatory and anti-inflammatory factors, including the adipokines leptin, adiponectin, resistin, and visfatin, as well as cytokines and chemokines, such as TNF-alpha, IL-6, monocyte chemoattractant protein 1, and others. Proinflammatory molecules produced by adipose tissue have been implicated as active participants in the development of insulin resistance and the increased risk of cardiovascular disease associated with obesity. In contrast, reduced leptin levels might predispose to increased susceptibility to infection caused by reduced T-cell responses in malnourished individuals. Altered adipokine levels have been observed in a variety of inflammatory conditions, although their pathogenic role has not been completely clarified.
SITE MAP
- Candida: Candida infectie - Vaginale infectie - CVS/ME: Chronische vermoeidheid Syndroom - Diabetische complicaties: Behandeling diabetische complicaties - Neuropathie - Retinopathie - Nefropathie - Bloeduiker stabilisatie - Hart en vaatziekten: Behandeling Cardiomyopathie (Hartfalen) - Treatment Cardiomyopathy (Heart Failure) - Hoge bloeddruk - Cholesterol verlaging - Aderverkalking (atherosclerose - arteriosclerose) - Levensverlenging: 100 jaren jong - DHEA - Melatonine - 65+ - Kanker: - Ondersteuningstherapie bij kanker - Artrose en artritis: - Artrose - Artritis - Arthrose und Arthritis - Fibromyalgie: - Behandeling Fibromyalgie: introductie - Urinewegen: - Prostaatklachten - Blaasontsteking - Voeding: Voeding wat is er mis mee - Melk BAH!! - Suiker vergif voor je lichaam - Aanvulling onvolwaardige voeding - Vitamine supplementen: Voedingssupplementen - Overgewicht: - Overgewicht Home page - SLIM Home page - Andere artikelen: - HPU - Astma - Multiple Sclerosis (MS) - Psoriasis - Plus - Depressie - Algemeen behandelingsforum - Orthomoleculaire Geneeskunde -
- Candida: Candida infectie - Vaginale infectie - CVS/ME: Chronische vermoeidheid Syndroom - Diabetische complicaties: Behandeling diabetische complicaties - Neuropathie - Retinopathie - Nefropathie - Bloeduiker stabilisatie - Hart en vaatziekten: Behandeling Cardiomyopathie (Hartfalen) - Treatment Cardiomyopathy (Heart Failure) - Hoge bloeddruk - Cholesterol verlaging - Aderverkalking (atherosclerose - arteriosclerose) - Levensverlenging: 100 jaren jong - DHEA - Melatonine - 65+ - Kanker: - Ondersteuningstherapie bij kanker - Artrose en artritis: - Artrose - Artritis - Arthrose und Arthritis - Fibromyalgie: - Behandeling Fibromyalgie: introductie - Urinewegen: - Prostaatklachten - Blaasontsteking - Voeding: Voeding wat is er mis mee - Melk BAH!! - Suiker vergif voor je lichaam - Aanvulling onvolwaardige voeding - Vitamine supplementen: Voedingssupplementen - Overgewicht: - Overgewicht Home page - SLIM Home page - Andere artikelen: - HPU - Astma - Multiple Sclerosis (MS) - Psoriasis - Plus - Depressie - Algemeen behandelingsforum - Orthomoleculaire Geneeskunde -
