Characterization of metalloprotease cleavage products of human articular cartilage

Zhen, Yuejun; Brittain, Isabelle J.; Laska, D. A.; Mitchell, Peter G.; Sumer, E.U.; Karsdal, Morten A.; Duffin, Kevin L.

doi:10.1002/art.23654

Cited by 138 publications

(138 citation statements)

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“…A further intriguing proteomic study was conducted to elucidate the target of MMPs and ADAMTSs in articular cartilage [20,55]. Human articular cartilage [55] or crude equine cartilage proteoglycan extract [20] was digested by the addition of exogenous metalloproteases, including MMP-2, -3, -8, -9, -12, and -13 and the aggrecanases ADAMTS-4 and ADAMTS-5.…”

Section: Proteolytic Enzymes and Their Regulatorsmentioning

confidence: 99%

“…Human articular cartilage [55] or crude equine cartilage proteoglycan extract [20] was digested by the addition of exogenous metalloproteases, including MMP-2, -3, -8, -9, -12, and -13 and the aggrecanases ADAMTS-4 and ADAMTS-5. Digestion products were identified by proteomic methods, and complete sequences of generated peptides were determined.…”

Section: Proteolytic Enzymes and Their Regulatorsmentioning

confidence: 99%

“…Digestion products were identified by proteomic methods, and complete sequences of generated peptides were determined. A wide variety of peptides, originating from collagen types I, II, and III, biglycan, prolargin, fibromodulin, fibronectin, decorin, COMP, cartilage intermediate-layer protein, megakaryocyte-stimulating factor, clusterin, mimecan, aggrecan, and lumican, were obtained [20,55]. MMP-2 was the most active protease used in the study, and the aggrecanases were the least active in generating peptides from cartilage digestion.…”

Section: Proteolytic Enzymes and Their Regulatorsmentioning

confidence: 99%

“…However, all of the proteases cleaved many types of cartilage ECM proteins [55]. Interestingly, IL-1β treatment generated many COMP neopeptides [14,20].…”

Section: Proteolytic Enzymes and Their Regulatorsmentioning

confidence: 99%

See 3 more Smart Citations

Chondrocyte secretome: a source of novel insights and exploratory biomarkers of osteoarthritis

Sanchez

Bay‐Jensen

Pap

et al. 2017

Osteoarthritis and Cartilage

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The extracellular matrix (ECM) of articular cartilage is comprised of complex networks of proteins and glycoproteins, all of which are expressed by its resident cell, the chondrocyte. Cartilage is a unique tissue given its complexity and ability to resist repeated load and deformation. The mechanisms by which articular cartilage maintains its integrity throughout our lifetime is not fully understood, however there are numerous regulatory pathways known to govern ECM turnover in response to mechanical stimuli. To further our understanding of this field, we envision that proteomic analysis of the secretome will provide information on how the chondrocyte remodels the surrounding ECM in response to load, in addition to providing information on the metabolic state of the cell. In this review, we attempt to summarize the recent mass spectrometry-based proteomic discoveries in healthy and diseased cartilage and chondrocytes, to facilitate the discovery of novel biomarkers linked to degenerative pathologies, such as osteoarthritis (OA).

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Section: Proteolytic Enzymes and Their Regulatorsmentioning

confidence: 99%

Section: Proteolytic Enzymes and Their Regulatorsmentioning

confidence: 99%

Section: Proteolytic Enzymes and Their Regulatorsmentioning

confidence: 99%

“…However, all of the proteases cleaved many types of cartilage ECM proteins [55]. Interestingly, IL-1β treatment generated many COMP neopeptides [14,20].…”

Section: Proteolytic Enzymes and Their Regulatorsmentioning

confidence: 99%

See 2 more Smart Citations

Chondrocyte secretome: a source of novel insights and exploratory biomarkers of osteoarthritis

Sanchez

Bay‐Jensen

Pap

et al. 2017

Osteoarthritis and Cartilage

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show abstract

“…Matrix metalloproteinases (MMPs) play an essential role in the degradation of ECM proteins such as collagens and proteoglycans. 7,8 Serum MMP-3, a key enzyme in ECM remodeling, is strongly elevated in AS patients. 9,10 Increased turnover of several different MMP-derived collagen species has been accepted as a main feature of AS.…”

Section: Introductionmentioning

confidence: 99%

Histopathological changes in supraspinous ligaments, ligamentum flava and paraspinal muscle tissues of patients with ankylosing spondylitis

Zhang

et al. 2014

Int J of Rheum Dis

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Objective: To examine the histopathological changes in spinal tissues of ankylosing spondylitis (AS) patients.Methods: Tissue samples from 10 AS patients and 10 control subjects were obtained. Hematoxylin and eosin, picrosirius, Masson and van Gieson stainings were utilized to determine the pathological changes in tissues. Ultrastructural alterations were examined by electronic microscopy. Proteoglycan levels were assessed by enzyme-linked immunosorbent assays (ELISA). Matrix metalloproteinase-3 (MMP-3), transforming growth factor-b1 (TGF-b1) and tumor necrosis factor-a (TNF-a) levels were evaluated by immunohistochemistry.Results: Our results demonstrate that the density of collagen fibrils was reduced in the supraspinous ligaments of AS tissue and fibrils were loosely and irregularly organized as compared to a regular distribution of collagen fibrils in controls. In ligamentum flava from AS patients, activated fibroblasts with enlarged nuclei were detected, while the number of elastic fibers was greatly decreased. Paraspinal muscle tissues of AS patients exhibited increased collagen fibril accumulation and atrophy. Significantly decreased proteoglycan and elevated MMP-3 levels were found in supraspinous ligament samples from AS patients (P < 0.01). Additionally, the levels of TGF-b1 in ligamentum flava and paraspinal muscle tissues of AS patients were increased (P < 0.01). The expression of TNF-a was also upregulated in the ligamentum flavum (P < 0.01), with no significant difference in the paraspinal muscle between control and AS patients (P > 0.05).Conclusions: Our findings reveal histopathological changes that occur in certain spinal tissues of AS patients and suggest that increased levels of MMP-3 and TGF-b1 may contribute to the pathogenesis of AS.

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Active involvement of alarmins S100A8 and S100A9 in the regulation of synovial activation and joint destruction during mouse and human osteoarthritis

Lent¹,

Blom²,

Schelbergen³

et al. 2012

Arthritis & Rheumatism

170

203

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Objective. To investigate whether alarmins S100A8 and S100A9 are involved in mediating cartilage destruction during murine and human osteoarthritis (OA).Methods. Two different murine models of OA that differed in terms of synovial activation were compared. Cartilage destruction was measured histologically. Synovial biopsy and serum samples from OA patients were derived from the Cohort Hip and Cohort Knee (CHECK) patients with symptomatic early OA. Expression of mediators in the synovium was measured by reverse transcription-polymerase chain reaction analysis and immunolocalization.Results. In collagenase-induced OA, which showed marked synovial activation, interleukin-1␤ was expressed at significant levels only during the early stages of disease, whereas S100A8 and S100A9 expression remained high for a prolonged period of time (up to day 21 after induction). In S100A9-knockout mice, we found a major impact of S100A8 and S100A9 on synovial activation (62% inhibition) and OA cartilage destruction (45-73% inhibition) as compared to wild-type controls. In contrast, in the surgically induced destabilized medial meniscus model, in which synovial involvement is scant, we found no role of S100A8 and S100A9 in the focal OA cartilage destruction. Examination of arthroscopic synovial biopsy samples from patients in the early symptomatic OA CHECK cohort revealed substantial levels of S100A8 and S100A9 messenger RNA and protein, which correlated significantly with synovial lining thickness, cellularity in the subintima, and joint destruction. Levels of S100A8/A9 serum protein were significantly enhanced (19%) at baseline in patients who had pronounced progression of joint destruction after 2 years.Conclusion. Our data suggest that the S100A8 and S100A9 proteins are crucially involved in synovial activation and cartilage destruction during OA and that high levels may predict joint destruction in humans with OA.

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Characterization of metalloprotease cleavage products of human articular cartilage

Cited by 138 publications

References 46 publications

Chondrocyte secretome: a source of novel insights and exploratory biomarkers of osteoarthritis

Chondrocyte secretome: a source of novel insights and exploratory biomarkers of osteoarthritis

Histopathological changes in supraspinous ligaments, ligamentum flava and paraspinal muscle tissues of patients with ankylosing spondylitis

Active involvement of alarmins S100A8 and S100A9 in the regulation of synovial activation and joint destruction during mouse and human osteoarthritis

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