Matrix Metalloproteinases: Role In Arthritis

Burrage, Peter S.; Mix, Kimberlee S.; Brinckerhoff, Constance E.

doi:10.2741/1817

Cited by 1,154 publications

(1,043 citation statements)

References 107 publications

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Section: Methodsmentioning

confidence: 99%

“…MMPs 1 and 13 were selected as they are known to be active against fibrillar collagens, including the predominant collagen type I 1, 28, 29, 30. MMP‐3 was selected as it degrades other minor proteins in tendon matrix, including collagens III, IV, IX, and X, and also proteoglycans and elastin 28, 29, 30, 31, 32, 33. The C1,2C (or COL 2 3/4C short) antibody detects the carboxy terminus of fragmented type I and II collagen, cleaved by collagenases MMP‐1, MMP‐8 or MMP‐13 21, 34, 35, 36, 37…”

Section: Methodsmentioning

confidence: 99%

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Tendon extracellular matrix damage, degradation and inflammation in response to in vitro overload exercise

Spiesz

Thorpe

Chaudhry

et al. 2015

Journal Orthopaedic Research

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The role of inflammation in tendon injury is uncertain and a topic of current interest. In vitro studies of tendon accelerated overload damage can serve as a valuable source of information on the early stages of tendinopathy. Viable fascicle bundles from bovine flexor tendons were subjected to cyclic uniaxial loading from 1–10% strain. Immuno‐staining for inflammatory markers and matrix degradation markers was performed on the samples after mechanical testing. Loaded samples exhibited visible extracellular matrix damage, with disrupted collagen fibers and fiber kinks, and notable damage to the interfascicular matrix. Inflammatory markers COX‐2 and IL‐6 were only expressed in the cyclically loaded samples. Collagen degradation markers MMP‐1 and C1,2C were colocalized in many areas, with staining occurring in the interfascicular matrix or the fascicular tenocytes. These markers were present in control samples, but staining became increasingly intense with loading. Little MMP‐3 or MMP‐13 was evident in control sections. In loaded samples, some sections showed intense staining of these markers, again localized to interfascicular regions. This study suggests that inflammatory markers may be expressed rapidly after tendon overload exercise. Interestingly, both inflammation and damage‐induced matrix remodeling seem to be concentrated in, or in the vicinity of, the highly cellular interfascicular matrix. © 2015 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 33:889–897, 2015.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Tendon extracellular matrix damage, degradation and inflammation in response to in vitro overload exercise

Spiesz

Thorpe

Chaudhry

et al. 2015

Journal Orthopaedic Research

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“…24 and 25; for review, see ref. 26), but this high molecular weight (HMW) gelatinase activity has not been characterized. Since NGAL has been shown to bind with MMP-9 (15), the purpose of this study was to examine the expression of NGAL in OA joints, using a combination of molecular, immunologic, and biochemical approaches to determine whether NGAL forms a complex with MMP-9, giving rise to the HMW gelatinase activity in OA SF (24).…”

mentioning

confidence: 99%

Neutrophil gelatinase–associated lipocalin is expressed in osteoarthritis and forms a complex with matrix metalloproteinase 9

Gupta¹,

Shukla²,

Cowland³

et al. 2007

Arthritis & Rheumatism

121

119

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Objective. Expression of matrix metalloproteinase 9 (MMP-9) is up-regulated in osteoarthritis (OA) and usually presents as multiple bands when synovial fluid (SF) from OA patients is analyzed by zymography. Among these bands is an ϳ125-130-kd band for high molecular weight (HMW) gelatinase, which has not been characterized. This study was undertaken to characterize the HMW MMP activity in OA SF.Methods. MMP activity in OA SF was determined by gelatin zymography. Recombinant MMPs were used to identify MMP activity on the zymogram. Western immunoblotting, immunoprecipitation, and immunodepletion analyses were performed using antibodies specific for human MMP-9 and human neutrophil gelatinase-associated lipocalin (NGAL). Human cartilage matrix degradation was determined by dimethylmethylene blue assay.Results. Zymographic analysis showed that the HMW gelatinase in OA SF comigrated with a purified NGAL-MMP-9 complex. Results of Western immunoblotting showed that the HMW gelatinase was also recognized by antibodies specific for human NGAL or human MMP-9. These same antibodies also immunoprecipitated the HMW gelatinase activity from OA SF. The NGAL-MMP-9 complex was reconstituted in vitro in gelatinase buffer. In the presence of NGAL, MMP-9 activity was stabilized; in the absence of NGAL, rapid loss of MMP-9 activity occurred. MMP-9-mediated release of cartilage matrix proteoglycans was significantly higher in the presence of NGAL (P < 0.05).Conclusion. Our findings demonstrate that the HMW gelatinase activity in OA SF represents a complex of NGAL and MMP-9. The ability of NGAL to protect MMP-9 activity is relevant to cartilage matrix degradation in OA and may represent an important mechanism by which NGAL may contribute to the loss of cartilage matrix proteins in OA.The developed world's aging population has experienced a dramatic increase in the incidence of joint dysfunction and osteoarthritis (OA), leading to a compromised quality of life. Aging, biomechanical stress, and oxidative stress, in addition to genetic factors and trauma, all appear to be associated with degenerative and progressive cartilage and bone changes in OA, particularly in the weight-bearing joints. Although OA is not considered an inflammatory disease by traditional standards, elevated levels of proinflammatory cytokines, such as interleukin-1␤ (IL-1␤) and tumor necrosis factor ␣, have been observed in OA synovial fluid (SF), supporting the notion that there is an inflammatory component associated with the pathogenesis of OA (for review, see refs. 1-3).The only cell type present in articular cartilage is the chondrocyte, which is embedded within an extracellular matrix (ECM) primarily composed of type II collagen and aggrecan. Chondrocytes arise from a mesenchymal progenitor cell and are responsible for the biosynthesis of ECM proteins and their transport into the space occupied by the ECM. Chondrocytes play an important role in cartilage homeostasis by maintaining the proper balance between anabolic pathways, which Supported in part by the NIH...

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“…The destruction of joint tissues that is a hallmark of rheumatoid arthritis (RA) and osteoarthritis (OA) is mediated largely by members of the matrix metalloproteinase (MMP) family of enzymes (1)(2)(3). At low expression levels, these zinc-dependent endopeptidases maintain connective tissue homeostasis in a wide range of biologic functions (4).…”

mentioning

confidence: 99%

“…In humans, the MMP family currently encompasses 23 unique members, which degrade all constituents of the extracellular matrix (ECM) (5). The MMPs can be subdivided into 6 main classes (1,4,5), consisting of the collagenases (MMPs 1, 8, and 13), the gelatinases (MMPs 2 and 9), the stromelysins (MMPs 3, 10, and 11), the matrilysins (MMPs 7 and 26), the membrane-type MMPs ( MMPs 14,15,16,17,24,and 25), and a diverse subgroup.…”

mentioning

confidence: 99%

Regulation of matrix metalloproteinase gene expression by a retinoid X receptor–specific ligand

Burrage¹,

Huntington²,

Sporn³

et al. 2007

Arthritis & Rheumatism

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Objective. To evaluate the effects of LG100268 (LG268), a synthetic ligand for the nuclear hormone receptor retinoid X receptor, on the expression of matrix metalloproteinase 1 (MMP-1) and MMP-13 induced by proinflammatory cytokines in a chondrocyte model.Methods. SW-1353 human chondrosarcoma cells were used to study the effects of LG268 on interleukin-1␤ (IL-1␤)-stimulated MMP production and collagen degradation. Gene expression was determined by quantitative real-time reverse transcriptionpolymerase chain reaction, and protein levels were determined by Western blot analysis. Collagen degradation was determined by an in vitro matrix destruction assay. The effects of LG268 on nuclear protein binding and histone acetylation were determined by electrophoretic mobility shift assay and chromatin immunoprecipitation assay, respectively.Results.LG268 treatment specifically antagonized the IL-1␤-mediated induction of MMP-1 and MMP-13 heterogeneous nuclear RNA, messenger RNA, and protein. The inhibitory effect of LG268 was found to be due to a decrease in the rate of MMP-1 and MMP-13 transcription.LG268 treatment also prevented the in vitro degradation of a type I collagen matrix by IL-1␤-treated SW-1353 cells. The inhibitory effect of LG268 on MMP-1 and MMP-13 transcription appears to be mediated, at least in part, through modulation of histone modification in regions of the MMP-1 and MMP-13 promoters that contain binding sites for activator protein 1 transcription factors.Conclusion. These data indicate that LG268 treatment selectively inhibits inflammatory cytokineinduced production of MMP-1 and MMP-13 at the level of gene transcription and blocks collagen destruction by proinflammatory cytokine-stimulated chondrocytic cells. This study is among the first to describe how rexinoids affect gene expression, and the findings suggest that the rexinoid class of compounds may have a future role in preventing the irreversible collagen destruction seen in the arthritides.The destruction of joint tissues that is a hallmark of rheumatoid arthritis (RA) and osteoarthritis (OA) is mediated largely by members of the matrix metalloproteinase (MMP) family of enzymes (1-3). At low expression levels, these zinc-dependent endopeptidases maintain connective tissue homeostasis in a wide range of biologic functions (4). However, abnormally high levels of MMP expression have been linked to multiple pathologic states, including tumor invasion, atherosclerosis, and the arthritides (4). In humans, the MMP family currently encompasses 23 unique members, which degrade all constituents of the extracellular matrix (ECM) (5). The MMPs can be subdivided into 6 main classes (1,4,5), consisting of the collagenases (MMPs 1, 8, and 13), the gelatinases (MMPs 2 and 9), the stromelysins (MMPs 3, 10, and 11), the matrilysins (MMPs 7 and 26), the membrane-type MMPs (MMPs 14,15,16,17,24,and 25), and a diverse subgroup.The collagenase subgroup is unique in its ability to cleave fibrillar collagens, and their enzymatic activity represents a rate-limiting step...

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Matrix Metalloproteinases: Role In Arthritis

Cited by 1,154 publications

References 107 publications

Tendon extracellular matrix damage, degradation and inflammation in response to in vitro overload exercise

Tendon extracellular matrix damage, degradation and inflammation in response to in vitro overload exercise

Neutrophil gelatinase–associated lipocalin is expressed in osteoarthritis and forms a complex with matrix metalloproteinase 9

Regulation of matrix metalloproteinase gene expression by a retinoid X receptor–specific ligand

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