Chondroprotective drugs in degenerative joint diseases

Verbruggen, G.

doi:10.1093/rheumatology/kei171

Cited by 136 publications

(62 citation statements)

References 117 publications

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“…In particular, IL-1b induces production of collagenase by synovial cells and of metalloproteinases by chondrocytes. 26 Another important characteristic of IL-1b is its toxicity for insulin-producing b-cells in Langerhans islets, supporting a role of IL-1b in the pathogenesis of insulin-dependent type I diabetes. 27,28 Similarly, IL-1b may be toxic for neurons and is involved in acute neurodegeneration and stroke.…”

Section: Caspase-1 and It Substrate Il-1bmentioning

confidence: 97%

Inflammatory caspases and inflammasomes: master switches of inflammation

2006

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Fifteen years have passed since the cloning and characterization of the interleukin-1b-converting enzyme (ICE/caspase-1), the first identified member of a family of proteases currently known as caspases. Caspase-1 is the prototypical member of a subclass of caspases involved in cytokine maturation termed inflammatory caspases that also include caspase-4 caspase -5, caspase -11 and caspase -12. Efforts to elucidate the molecular mechanisms involved in the activation of these proteases have uncovered an important role for the NLR family members, NALPs, NAIP and IPAF. These proteins promote the assembly of multiprotein complexes termed inflammasomes, which are required for activation of inflammatory caspases. This article will review some evolutionary aspects, biochemical evidences and genetic studies, underlining the role of inflammasomes and inflammatory caspases in innate immunity against pathogens, autoinflammatory syndromes and in the biology of reproduction. Inflammatory CaspasesThe history of caspases began with the identification of an aspartate-specific protease activity involved in the conversion of the 31 kDa proIL-1b precursor to its active 17 kDa biologically active form, 1,2 and the identification of caspase-1 as the protease responsible for proIL-1b maturation. 3,4 The subsequent discovery of ced-3, that shares similarities with caspase-1 and which is involved in programmed cell death (PCD) in Caenorhabditis elegans, suggested that caspases might play fundamental roles in apoptosis. 5 As reviewed in the papers accompanying this issue of Cell Death and Differentiation, the role of apoptotic caspases in C. elegans and in vertebrates is crucial and deal with many facets of cell biology, development and diseases. In this review, we will focus on a subset of caspases present only in vertebrates and known as inflammatory caspases.Inflammatory caspases (also known as group I caspases) are encoded by three main genes in humans caspase-1, caspase-4 and caspase-5 and three main genes in mouse, caspase-1, caspase-11 and caspase-12. 6,7 In mammals, these caspases are characterized by the presence of a CARD domain at the N-terminus (Figure 1a). Human, chimp and mouse inflammatory caspases share significant similarity and are organized in a single locus (Figure 1c). Phylogenetic analysis of the conserved CARD domain suggests that the inflammatory caspases can be separated in evolutionaryrelated clusters (Figure 1b). The caspase-1 cluster contains caspase-1 and four other genes encoding decoy caspases: cop, inca1, inca2 and iceberg. These decoy caspase-1-like genes are absent in the mouse genome, suggesting that they have arisen recently by duplication of caspase-1. Although human and mouse caspase-1 are likely orthologues, sequence analysis suggests that human caspase-4 and caspase-5 have originated from a duplication of caspase-11. 7 However, the human caspase-12 gene, which in the chimp genome contains an SHG box important for it enzymatic activity, 8 evolved towards an enzymatically inactive form at some stage...

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Section: Caspase-1 and It Substrate Il-1bmentioning

confidence: 97%

Inflammatory caspases and inflammasomes: master switches of inflammation

2006

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“…Currently there exists no accepted medical treatment with structure or disease modification in OA (24)(25)(26)(27)(28)(29)(30)(31), despite the high and vastly increasing number of patients with a need to be treated. In this context, quantitative MRI can help to identify promising drug targets (by identifying tissue components that change first and are responsible for changes in other tissues) and, in particular, to monitor structural effects of drugs in order to prove their effectiveness.…”

Section: Rationale For Quantitative Mri Of Cartilage and Bone In Ostementioning

confidence: 99%

Quantitative MRI of cartilage and bone: degenerative changes in osteoarthritis

2006

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Magnetic resonance imaging (MRI) and quantitative image analysis technology has recently started to generate a great wealth of quantitative information on articular cartilage and bone physiology, pathophysiology and degenerative changes in osteoarthritis. This paper reviews semiquantitative scoring of changes of articular tissues (e.g. WORMS ¼ whole-organ MRI scoring or KOSS ¼ knee osteoarthritis scoring system), quantification of cartilage morphology (e.g. volume and thickness), quantitative measurements of cartilage composition (e.g. T 2 , T 1rho , T 1Gd ¼ dGEMRIC index) and quantitative measurement of bone structure (e.g. app. BV/TV, app. TbTh, app. Tb.N, app. Tb.Sp) in osteoarthritis. For each of these fields we describe the hardware and MRI sequences available, the image analysis systems and techniques used to derive semiquantitative and quantitative parameters, the technical accuracy and precision of the measurements reported to date and current results from cross-sectional and longitudinal studies in osteoarthritis. Moreover, the paper summarizes studies that have compared MRI-based measurements with radiography and discusses future perspectives of quantitative MRI in osteoarthritis. In summary, the above methodologies show great promise for elucidating the pathophysiology of various tissues and identifying risk factors of osteoarthritis, for developing structure modifying drugs (DMOADs) and for combating osteoarthritis with new and better therapy. Copyright # 2006 John Wiley & Sons, Ltd.KEYWORDS: osteoarthritis; joint; cartilage; bone; magnetic resonance imaging; knee; image analysis; disease-modifying drugs RATIONALE FOR QUANTITATIVE MRI OF CARTILAGE AND BONE IN OSTEOARTHRITISThe health and integrity of diarthrodial (synovial) joints are prerequisites for pain-free movement and have a major impact on the quality of life. However, the population of individuals above the age of 65 years is rapidly growing and 70% of the women and 60% of the men aged 65 years or older suffer from degenerative joint disease [¼ osteoarthritis (OA)] (1-7). OA has been defined by the American College of Rheumatology (ACR) as a 'heterogeneous group of conditions that leads to joint symptoms and signs which are associated with defective integrity of articular cartilage, in addition to related changes in the underlying bone at the joint margins'. It remains an open question whether the initial changes take place in cartilage or bone or other articular tissues and, more importantly, what the causal relationship between these changes is (5-19). Also, within each NMR IN BIOMEDICINE NMR Biomed. 2006; 19: 822-854 Published online in Wiley InterScience (www.interscience.wiley.com). DOI:10.1002/nbm.1063 narrowing; JSW, joint space width; K, knee; KLG, Kellgren Lawrence grade; KOSS, knee osteoarthritis scoring system; LF, lateral femoral condyle; LT, lateral tibia; MRI, magnetic resonance imaging; MF, medial femoral condyle; MT, medial tibia; OA, osteoarthritis; OAI, Osteoarthritis Initiative; P, patella; PGs, proteoglycans;...

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“…Hence, there has been a continuous search for new and better drugs for OA. There has been increase in the use of symptomatic slow acting drugs such as glucosamine, CS and diacetylrhein (diacerein) [7]. These drugs could favor anabolic processes in the OA cartilage and contribute to a delayed progression of the disease via inhibition of the catabolic processes [8].…”

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confidence: 99%