- Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, Kington RS, Lane NE, Nevitt MC, Zhang Y, Sowers M, McAlindon T, Spector TD, Poole AR, Yanovski SZ, Ateshian G, Sharma L, Buckwalter JA, Brandt KD, Fries JF. Ann Intern Med. 2000 Oct 17;133(8):635-46. Osteoarthritis: new insights. Part 1: the disease and its risk factors
Osteoarthritis is the most common form of arthritis, affecting millions of people in the United States. It is a complex disease whose etiology bridges biomechanics and biochemistry. Evidence is growing for the role of systemic factors (such as genetics, dietary intake, estrogen use, and bone density) and of local biomechanical factors (such as muscle weakness, obesity, and joint laxity). These risk factors are particularly important in weight-bearing joints, and modifying them may present opportunities for prevention of osteoarthritis-related pain and disability.[Article]
- Felson DT, Lawrence RC, Hochberg MC, McAlindon T, Dieppe PA, Minor MA, Blair SN, Berman BM, Fries JF, Weinberger M, Lorig KR, Jacobs JJ, Goldberg V. Ann Intern Med. 2000 Nov 7;133(9):726-37.
Part 2 focuses on treatment approaches; evidence for the efficacy of commonly used oral therapies is reviewed and information on alternative therapies, including nutriceuticals and acupuncture, is presented. Biomechanical interventions, such as exercise and bracing, and behavioral interventions directed toward enhancing self-management are reviewed. Current surgical approaches are described and probable future biotechnology-oriented approaches to treatment are suggested.[Article]
- Kurz B, Lemke AK, Fay J, Pufe T, Grodzinsky AJ, SchŁnke M. Ann Anat. 2005 Nov;187(5-6):473-85. Pathomechanisms of cartilage destruction by mechanical injury
Mechanical injury is considered to be a major inductor of articular cartilage destruction and therefore a risk factor for the development of secondary osteoarthritis. Mechanical injury induces damage to the tissue matrix directly or mediated by chondrocytes via expression of matrix-degrading enzymes and reduction of biosynthetic activity. As a consequence the mechanical properties of cartilage change.[Abstract]
- Lane Smith R, Trindade MC, Ikenoue T, Mohtai M, Das P, Carter DR, Goodman SB, Schurman DJ. Biorheology. 2000;37(1-2):95-107. Effects of shear stress on articular chondrocyte metabolism
The articular cartilage of diarthrodial joints experiences a variety of stresses, strains and pressures that result from normal activities of daily living. In normal cartilage, the extracellular matrix exists as a highly organized composite of specialized macromolecules that distributes loads at the bony ends. The chondrocyte response to mechanical loading is recognized as an integral component in the maintenance of articular cartilage matrix homeostasis. With inappropriate mechanical loading of the joint, as occurs with traumatic injury, ligament instability, bony malalignment or excessive weight bearing, the cartilage exhibits manifestations characteristic of osteoarthritis. Breakdown of cartilage in osteoarthritis involves degradation of the extracellular matrix macromolecules and decreased expression of chondrocyte proteins necessary for normal joint function.[Abstract]
- Tchetina EV, Squires G, Poole AR. J Rheumatol. 2005 May;32(5):876-86. Increased type II collagen degradation and very early focal cartilage degeneration is associated with upregulation of chondrocyte differentiation related genes in early human articular cartilage lesions
Very early focal degeneration in knee articular cartilage is accompanied by upregulation of collagenase activity and expression of genes associated with chondrocyte terminal differentiation and matrix degradation. Thus chondrocyte differentiation may be closely related to the very early development of cartilage degeneration such as occurs in OA.[Abstract]
- Squires GR, Okouneff S, Ionescu M, Poole AR. Arthritis Rheum. 2003 May;48(5):1261-70. The pathobiology of focal lesion development in aging human articular cartilage and molecular matrix changes characteristic of osteoarthritis
These results demonstrate that lesions seen in aging exhibit molecular changes in matrix turnover similar to those seen in OA articular cartilage at arthroplasty, but not in healthy normal aging cartilage. The direct relationships between type II collagen cleavage and denaturation and the inverse relationship between type II collagen content and cleavage or denaturation implicate collagenase activity and damage to collagen in this loss of collagen during lesion developmen.[Article]
- Henrotin YE, Bruckner P, Pujol JP Osteoarthritis Cartilage. 2003 Oct;11(10):747-55. The role of reactive oxygen species in homeostasis and degradation of cartilage
This review of the literature supports the concept that ROS are not only deleterious agents involved in cartilage degradation, but that they also act as integral factors of intracellular signaling mechanisms.[Abstract]
- Bonet ML, Granados N, Palou A. Curr Drug Targets. 2011 Dec;12(14):2103-28. Molecular players at the intersection of obesity and osteoarthriti
Dysregulated production of adipose tissue-derived inflammatory mediators, hyperlipidemia, and increased systemic oxidative stress are conditions frequently associated with obesity that may favor joint degeneration.[Abstract]
- Yudoh K, Nguyen vT, Nakamura H, Hongo-Masuko K, Kato T, Nishioka K. Arthritis Res Ther. 2005;7(2):R380-91. Epub 2005 Jan 26. Potential involvement of oxidative stress in cartilage senescence and development of osteoarthritis: oxidative stress induces chondrocyte telomere instability and downregulation of chondrocyte function
Oxidative stress leads to increased risk for osteoarthritis (OA) but the precise mechanism remains unclear.[Article]
- Zhuo Q, Yang W, Chen J, Wang Y. Nat Rev Rheumatol. 2012 Dec;8(12):729-37. doi: 10.1038/nrrheum.2012.135. Metabolic syndrome meets osteoarthriti
In this Review, we summarize the shared mechanisms of inflammation, oxidative stress, common metabolites and endothelial dysfunction that characterize the aetiologies of OA and MetS, and nominate metabolic OA as the fifth component of MetS. We also describe therapeutic opportunities that might arise from uniting these concepts.[Abstract]
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.
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.
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 GŲ 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.
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.
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.
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.
Overall, there is a growing scientific rationale for the use of dietary supplements as adjuncts in the treatment of inflammatory disorders such as rheumatoid arthritis and osteoarthritis.[Abstract]
Maagdarmstoornissen: Candida infectie - Prikkelbaredarmsyndroom - Crohn - Colitus Ulcerosa - CVS/ME: Chronische vermoeidheid Syndroom - Diabetische complicaties: Bloeduiker stabilisatie - Neuropathie - Retinopathie - Nefropathie - Hart- en vaatziekten: Cardiomyopathie en Hartfalen - Hoge bloeddruk - Cholesterol verlaging - Aderverkalking (atherosclerose) - Spataderen - Levensverlenging: 100 jaren jong - DHEA - Melatonine - 65+ - Kanker: - Ondersteuningstherapie bij kanker - Bot en gewrichtsaandoeningen: - Artrose - Artritis - Osteoporose - Fibromyalgie: - Fibromyalgie - Urinewegaandoeningen: - Prostaatklachten - Blaasontsteking - Vrouwenklachten: Menopauze - Premenstrueelsyndroom - Overgewicht: - Overgewicht - SLIM - Oogaandoeningen: Staar - Slecht zien Andere artikelen: - HPU - Astma - Multiple Sclerose - Psoriasis - Depressie