MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis

Tchetverikov, I.; Lohmander, L. Stefan; Verzijl, Nicole; Huizinga, T.; TeKoppele, J.M.; Hanemaaijer, Roeland; DeGroot, Jeroen

doi:10.1136/ard.2004.022434

Cited by 182 publications

(133 citation statements)

References 41 publications

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“…Supernatants from digestions with these enzymes were analyzed via proteomics methods to determine specific sites of cleavage of cartilage proteins by different metalloproteases, for better understanding of their selectivities and to measure the release of peptides that may serve as useful biomarkers of cartilage degradation. The metalloproteases utilized in this study have been reported to be overexpressed and active in arthritic cartilage (11,18,30). Therefore, determination of their substrates and products may lead to a better understanding of the potential role of metalloproteases in arthritis, and also may help in the identification of new biomarkers of cartilage degradation.…”

mentioning

confidence: 96%

Characterization of metalloprotease cleavage products of human articular cartilage

Zhen¹,

Brittain²,

Laska³

et al. 2008

Arthritis & Rheumatism

141

130

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Objective. To identify, characterize, and compare proteolysis peptide products generated by metalloprotease digests of human articular cartilage.Methods. Human articular cartilage was digested by the addition of exogenous metalloproteases, including matrix metalloproteinases 2, 3, 8, 9, 12, and 13 and aggrecanases ADAMTS-4 and ADAMTS-5. Proteolyzed peptide products were identified by proteomics methods using mass spectrometry.Results. Complete sequences of the peptides proteolyzed from human articular cartilage, including Nand C-termini and hydroxylated posttranslational modifications, were determined. A wide variety of peptides, originating from types I, II, and III collagen, biglycan, prolargin, fibromodulin, fibronectin, decorin, cartilage oligomeric matrix protein, cartilage intermediate-layer protein, megakaryocyte-stimulating factor, mimecan, aggrecan, and lumican, was analyzed following metalloprotease digestion. Release of peptides varied as a function of time, enzyme specificity, and abundance. Specific type II collagen peptide biomarkers, including those containing the three-quarter-length fragment cleavage site and those containing the domains for helical peptide of type II collagen and C-telopeptide of type II collagen, were observed after release by selected proteases.Conclusion. The use of intact cartilage instead of purified protein substrates in the assay allowed for the identification of novel potential substrates and cleavage sites for individual enzymes under more physiologically relevant conditions. Characterization of these cartilage matrix peptides may help in the development of pharmacodynamic biomarkers of cartilage degradation, and also may contribute to an understanding of the bioactive peptides important in chondrocyte signaling.Osteoarthritis (OA) and rheumatoid arthritis (RA) are typified by biologic changes in the articular cartilage that lead to cartilage degradation and joint space narrowing (1,2). Articular cartilage is composed of 2 primary matrix proteins, type II collagen and aggrecan, as well as a number of other matrix proteins that provide structural functions such as rigidity, flexibility, and compression damping. In addition, the cartilage matrix influences chondrocyte function through integrin receptor signaling, initiated via ligation of either intact matrix molecules or peptide fragments resulting from proteolytic activity (3).In arthritis, an imbalance of chondrocyte matrix synthesis and degradation leads to a net loss of matrix, and eventually to joint impairment. In OA, the excessive degradation is primarily due to the action of proteases released by chondrocytes, synovial cells, and macrophages (4). Numerous serine proteases and metalloproteases are overexpressed by these cells during the disease process, but specific metalloproteases, including the collagenase matrix metalloproteinase 13 (MMP-13) and the aggrecanase ADAMTS-5, are thought to be especially important for initiating and promoting cartilage matrix degradation in OA (5,6). MMP-13 cleaves type II collage...

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mentioning

confidence: 96%

Characterization of metalloprotease cleavage products of human articular cartilage

Zhen¹,

Brittain²,

Laska³

et al. 2008

Arthritis & Rheumatism

141

130

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“…Aggrecan breakdown in degenerative joints is typically the result of proteolytic cleavage, and aggrecanases and matrix metalloproteinases (MMPs) are the primary proteases responsible for aggrecan cleavage in pathologic conditions [40]. Additionally, MMPs are capable of degrading intact Type II collagen into large fragments that can then be further degraded by gelatinases [42].…”

Section: Introductionmentioning

confidence: 99%

Intraarticular Matrix Metalloproteinases and Aggrecan Degradation Are Elevated After Articular Fracture

Haller

Swearingen

Partridge

et al. 2015

Clin Orthop Relat Res

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Background Posttraumatic osteoarthritis (OA) is a variant of OA that can develop after articular injury. Although the mechanism(s) of posttraumatic OA are uncertain, the presence and impact of postinjury proteolytic enzymes on articular cartilage remain unknown. To our knowledge, there are no studies that evaluate the presence of matrix metalloproteinases (MMPs) or aggrecan degradation after articular fracture.Questions/purposes (1) Are MMP concentrations and aggrecan degradation elevated after intraarticular fracture? (2) Are MMP concentrations and aggrecan degradation greater in high-energy injuries compared with low-energy injuries? (3) Do the concentrations of these biomarkers remain elevated at a secondary aspiration? Methods Between December 2011 and June 2013, we prospectively enrolled patients older than 18 years of age with acute tibial plateau fracture. Exclusion criteria included age older than 60 years, preexisting knee OA, injury greater than 24 hours before evaluation, contralateral knee injury, history of autoimmune disease, open fracture, and non-English-speaking patients. During the enrollment period, we enrolled 45 of the 91 (49%) tibial plateau fractures treated at our facility. Knee synovial fluid aspirations were obtained from both the injured and uninjured knees; two patients received aspirations in the emergency department and the remaining patients received aspirations in the operating room. Twenty patients who underwent spanning external fixator followed by definitive fixation were aspirated during both surgical procedures. MMP-1, -2, -3, -7, -9, -10, -12, and -13 concentrations were quantified using multiplex assays. Aggrecan degradation was quantified using sandwich enzyme-linked immunosorbent assay. Results There were higher concentrations of MMP-1 (3.89 ng/mL [95% confidence interval {CI}, 2.37-6.37] versus 0.37 ng/mL [95% CI, 0.23-0.61], p \ 0.001), MMP-3The institution of one or more of the authors (JMH, TFH) has received peer-reviewed research grant funding from the Orthopedic Trauma Association, LS Peery Foundation, and AO North America for this project. One of the authors certifies that he (TFH), or a member of his immediate family, has signed an agreement with DePuy Synthes (Warsaw, IN, USA) for consulting activities not related to the current study, and has not received payments or benefits, during the study period. One or more of the authors (CAS, KT) are employed at Eli Lilly (Indianapolis, IN, USA). All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research1 editors and board members are on file with the publication and can be viewed on request. Clinical Orthopaedics and Related Research1 neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDAapproval status, of any drug or device prior to clinical use. Each author certifies that his or her institution approved or waived approval for the reporting of this investigation and that all inves...

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“…These proteins include glycoprotein debris and collagen fragments derived from destructed cartilaginous tissue and enzymes such as metalloproteinase, collagenase and proinflammatory cytokines (interleukin-1, interleukin-1, tumour necrosis factor , etc) (Yoshihara Y et al, 2000;Hedbom E and Hauselmann HJ, 2002;Tchetverikov I et al, 2005). All of these proteins in synovial fluid might reflect the pathological status of the knees.…”

Section: Analysis Of Joint Fluidmentioning

confidence: 99%

Knee Health Promotion Option for Osteoarthritic Knee: Cartilage Regeneration is Possible

Lyu¹,

Liu²,

Tseng³

et al. 2012

Osteoarthritis - Diagnosis, Treatment and Surgery

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MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis

Cited by 182 publications

References 41 publications

Characterization of metalloprotease cleavage products of human articular cartilage

Characterization of metalloprotease cleavage products of human articular cartilage

Intraarticular Matrix Metalloproteinases and Aggrecan Degradation Are Elevated After Articular Fracture

Knee Health Promotion Option for Osteoarthritic Knee: Cartilage Regeneration is Possible

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