Coincubation of Bovine Synovial or Capsular Tissue with Cartilage Generates a Soluble “Aggrecanase” Activity

Vankemmelbeke, Mireille; Mz, Ilic; Cj, Handley; Cg, Knight; Dj, Buttle

doi:10.1006/bbrc.1999.0266

Cited by 24 publications

(23 citation statements)

References 36 publications

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“…However other tissues, such as bovine fibroblasts, joint capsules, and tendon, are also able to produce aggrecanase activity (27)(28)(29)(30). The regulation of both aggrecanase-1 and -2 in human synoviocytes and synovium remains poorly defined.…”

Section: Figurementioning

confidence: 99%

Expression and Regulation of Aggrecanase in Arthritis: The Role of TGF-β

Yamanishi

Boyle

Clark

et al. 2002

The Journal of Immunology

165

128

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Aggrecanases are key matrix-degrading enzymes that act by cleaving aggrecan at the Glu373-Ala374 site. While these fragments have been detected in osteoarthritis (OA) and rheumatoid arthritis (RA) cartilage and synovial fluid, no information is available on the regulation or expression of the two key aggrecanases (aggrecanase-1 and aggrecanase-2) in synovial tissue (ST) or fibroblast-like synoviocytes (FLS). The aggrecanase-1 gene was constitutively expressed by both RA and OA FLS. Real-time PCR demonstrated that TGF-β significantly increased aggrecanase-1 gene expression in FLS. Aggrecanase-1 induction peaked after 24 h of TGF-β stimulation. The expression of aggrecanase-1 mRNA was significantly greater in RA ST than in OA or nonarthritis ST. Aggrecanase-2 mRNA and protein were constitutively produced by nonarthritis, OA, and RA FLS but were not increased by IL-1, TNF-α, or TGF-β. Furthermore, OA, RA, and nonarthritis ST contained similar amounts of immunoreactive aggrecanase-2. The major form of the aggrecanase-2 enzyme was 70 kDa in nonarthritis ST, whereas a processed 53-kDa form was abundant in RA ST. Therefore, aggrecanase-1 and -2 are differentially regulated in FLS. Both are constitutively expressed, but aggrecanase-1 is induced by cytokines, especially TGF-β. In contrast, aggrecanase-2 protein may be regulated by a post-translational mechanism in OA and RA ST. Synovial and FLS production of aggrecanase can contribute to cartilage degradation in RA and OA.

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Section: Figurementioning

confidence: 99%

Expression and Regulation of Aggrecanase in Arthritis: The Role of TGF-β

Yamanishi

Boyle

Clark

et al. 2002

The Journal of Immunology

165

128

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“…However, cartilage injury alone does not appear to involve sustained cell-mediated matrix degradation (7,16,19). Since the pathogenesis of OA is known to involve interactions between different tissue and cell types within a joint, we and others have studied in vitro models that include interactions between injured cartilage and inflammatory cytokines, via direct cytokine treatment (21) or indirectly by coincubation of injured cartilage with synovial tissue (22,23).…”

mentioning

confidence: 99%

Mechanical injury potentiates proteoglycan catabolism induced by interleukin‐6 with soluble interleukin‐6 receptor and tumor necrosis factor α in immature bovine and adult human articular cartilage

Sui¹,

Lee²,

DiMicco³

et al. 2009

Arthritis & Rheumatism

110

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Objective. Traumatic joint injury can damage cartilage and release inflammatory cytokines from adjacent joint tissue. The present study was undertaken to study the combined effects of compression injury, tumor necrosis factor ␣ (TNF␣), and interleukin-6 (IL-6) and its soluble receptor (sIL-6R) on immature bovine and adult human knee and ankle cartilage, using an in vitro model, and to test the hypothesis that endogenous IL-6 plays a role in proteoglycan loss caused by a combination of injury and TNF␣.Methods. Injured or uninjured cartilage disks were incubated with or without TNF␣ and/or IL-6/sIL-6R. Additional samples were preincubated with an IL-6-blocking antibody Fab fragment and subjected to injury and TNF␣ treatment. Treatment effects were assessed by histologic analysis, measurement of glycosaminoglycan (GAG) loss, Western blot to determine proteoglycan degradation, zymography, radiolabeling to determine chondrocyte biosynthesis, and Western blot and enzyme-linked immunosorbent assay to determine chondrocyte production of IL-6.Results. In bovine cartilage samples, injury combined with TNF␣ and IL-6/sIL-6R exposure caused the most severe GAG loss. Findings in human knee and ankle cartilage were strikingly similar to those in bovine samples, although in human ankle tissue, the GAG loss was less severe than that observed in human knee tissue. Without exogenous IL-6/sIL-6R, injury plus TNF␣ exposure up-regulated chondrocyte production of IL-6, but incubation with the IL-6-blocking Fab significantly reduced proteoglycan degradation.Conclusion. Our findings indicate that mechanical injury potentiates the catabolic effects of TNF␣ and IL-6/sIL-6R in causing proteoglycan degradation in human and bovine cartilage. The temporal and spatial evolution of degradation suggests the importance of transport of biomolecules, which may be altered by overload injury. The catabolic effects of injury plus TNF␣ appeared partly due to endogenous IL-6, since GAG loss was partially abrogated by an IL-6-blocking Fab.Osteoarthritis (OA) is a highly prevalent joint disease characterized by progressive degradation and loss of articular cartilage. Joint injury in young adults dramatically increases the risk for developing OA (1,2). Acute knee injury, such as anterior cruciate ligament tear, can subject cartilage to high mechanical stress and is accompanied by an increase in synovial fluid levels of matrix metalloproteinase 3 (MMP-3) (3) and multiple

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“…The joint capsule is known to be a potential source of aggrecanase activity (Ilic et al, 2000), and capsule has the capacity to increase breakdown of cartilage proteoglycan in vitro, even when the cartilage tissue has been killed. This suggests the action of a capsulederived aggrecanase on cartilage (Vankemmelbeke et al, 1999) (Table 4).…”

Section: The Joint Capsule: Protease and Inflammatory Mediator Generamentioning

confidence: 98%

“…In rheumatoid arthritis synovitis is associated with hyperplasia of the synoviocytes, an infiltration of mononuclear cells including B cells, T cells and macrophages into the synovial sublining, and the formation of a locally invasive pannus (Lee & Weinblatt, 2001). A number of studies have shown that in arthritic pathologies the synovial expression of a number of proteases, including MMP collagenases, ADAMTS aggrecanases and MMP-3, is increased as are the levels of these proteases in the synovial fluid (Hulejová et al, 2007;Smeets et al, 2003;Tchetverikov et al, 2004;Vankemmelbeke et al, 2001;Vankemmelbeke, Ilic, Handley, Knight, & Buttle, 1999). In vitro studies have implicated synovium-derived factors, in particular proinflammatory cytokines (Fell & Jubb, 1977;Saklatvala, Pilsworth, Sarsfield, Gavrilovic, & Heath, 1984) and proteases (Vankemmelbeke et al, 1999(Vankemmelbeke et al, , 2001) as mediators of cartilage destruction.…”

Section: Synovium: Inflammation Hyperplasia Pannus Formation and Prmentioning

confidence: 99%

“…Late-stage rheumatoid arthritis is associated with the development of bone erosions and osteoporosis, with multinucleated osteoclasts within the osteolytic lesions Ilic et al (2000), Vankemmelbeke et al (1999) (Eggelmeijer et al, 1993;Ishikawa, Ohno, & Hirohata, 1984;Magaro et al, 1991). Osteoarthritis is associated with bone sclerosis and collagen type I synthesis and metabolism (Mansell & Bailey, 1998;Mansell, Tarlton, & Bailey, 1997;Seibel, Duncan, & Robins, 1989).…”

Section: Bone: Altered Metabolism and Extracellular Matrix Proteolysismentioning

confidence: 99%

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The role of proteases in pathologies of the synovial joint

Jones¹,

Riley²,

Buttle³

2008

The International Journal of Biochemistry & Cell Biology

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Synovial (diarthrodial) joints are employed within the body to provide skeletal mobility and have a characteristic structure adapted to provide a smooth almost frictionless surface for articulation. Pathologies of the synovial joint are an important cause of patient morbidity and can affect each of the constituent tissues. A common feature of these pathologies is degenerative changes in the structure of the tissue which is mediated, at least in part, by proteolytic activity. Most tissues of the synovial joint are composed primarily of extracellular matrix and key pathological roles in the degeneration of this matrix are performed by metalloproteinases such as matrix metallproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS). However, other proteases such as cathepsin K are likely to play an important role, especially in bone turnover. In addition to the cleavage of structural proteins, proteolytic activities are employed to regulate the activity of other proteases, growth factors, cytokines and other inflammatory mediators. Proteases combine to form complex regulatory networks, the correct functioning of which is required for tissue homeostasis and the imbalance of which may be a feature of pathology. A precise understanding of the proteases involved in these networks is required for a true understanding of the associated pathology.

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Coincubation of Bovine Synovial or Capsular Tissue with Cartilage Generates a Soluble “Aggrecanase” Activity

Cited by 24 publications

References 36 publications

Expression and Regulation of Aggrecanase in Arthritis: The Role of TGF-β

Expression and Regulation of Aggrecanase in Arthritis: The Role of TGF-β

Mechanical injury potentiates proteoglycan catabolism induced by interleukin‐6 with soluble interleukin‐6 receptor and tumor necrosis factor α in immature bovine and adult human articular cartilage

The role of proteases in pathologies of the synovial joint

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