Brevican Is Degraded by Matrix Metalloproteinases and Aggrecanase-1 (ADAMTS4) at Different Sites

Nakamura, Hiroyuki; Fujii, Yutaka; Inoki, Isao; Sugimoto, Kotaro; Tanzawa, Kazuhiko; Matsuki, Hitoshi; Miura, Ryu; Yamaguchi, Yu; Okada, Yasunori

doi:10.1074/jbc.m003875200

Cited by 155 publications

(132 citation statements)

References 35 publications

(52 reference statements)

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“…Although an overall reduction in TIMP protein levels would provide an environment more permissible to metalloproteinase activity, a shift in TIMP balance toward TIMP-1 may also be of significance, since TIMP-1 differs in its activity compared with that of the other TIMP members (62). Unlike other TIMP members, TIMP-1 shows little inhibitory activity toward MMP-19 or the membrane-type MMPs, MMPs 14,15,16,and 24 (20).…”

Section: Discussionmentioning

confidence: 99%

“…The ADAMTS family consists of 19 human gene products, which include N-terminal procollagen propeptidases (ADAMTS-2, -3, and -14) and aggrecanases (ADAMTS-1, -4, -5, -8, -9, and -15) that appear to participate in early degradative events of arthritic cartilage, and are implicated in tendon-matrix turnover (11)(12)(13). Aggrecanases cleave aggrecan at characteristic sites located C-terminal to a glutamate residue (14), but some members also cleave related proteoglycans such as versican and brevican at equivalent sites (15)(16)(17). ADAMTS-4 has also been shown to cleave other, nonproteoglycan ECM components such as cartilage oligomeric matrix protein (18), fibromodulin, and decorin (19).…”

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confidence: 99%

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Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon

Jones¹,

Corps²,

Pennington³

et al. 2006

Arthritis & Rheumatism

256

284

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Objective. To profile the messenger RNA (mRNA) expression for the 23 known genes of matrix metalloproteinases (MMPs), 19 genes of ADAMTS, 4 genes of tissue inhibitors of metalloproteinases (TIMPs), and ADAM genes 8, 10, 12, and 17 in normal, painful, and ruptured Achilles tendons.Methods. Tendon samples were obtained from cadavers or from patients undergoing surgical procedures to treat chronic painful tendinopathy or ruptured tendon. Total RNA was extracted and mRNA expression was analyzed by quantitative real-time reverse transcription-polymerase chain reaction, normalized to 18S ribosomal RNA.Results. In comparing expression of all genes, the normal, painful, and ruptured Achilles tendon groups each had a distinct mRNA expression signature. Three mRNA were not detected and 14 showed no significant difference in expression levels between the groups. Statistically significant (P < 0.05) differences in mRNA expression, when adjusted for age, included lower levels of MMPs 3 and 10 and TIMP-3 and higher levels of ADAM-12 and MMP-23 in painful compared with normal tendons, and lower levels of MMPs 3 and 7 and TIMPs 2, 3, and 4 and higher levels of ADAMs 8 and 12, MMPs 1, 9, 19, and 25, and TIMP-1 in ruptured compared with normal tendons.Conclusion. The distinct mRNA profile of each tendon group suggests differences in extracellular proteolytic activity, which would affect the production and remodeling of the tendon extracellular matrix. Some proteolytic activities are implicated in the maintenance of normal tendon, while chronically painful tendons and ruptured tendons are shown to be distinct groups. These data will provide a foundation for further study of the role and activity of many of these enzymes that underlie the pathologic processes in the tendon.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon

Jones¹,

Corps²,

Pennington³

et al. 2006

Arthritis & Rheumatism

256

284

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“…In previous studies it has been shown that recombinant human ADAMTS5 degrades aggrecan at mostly identical sites than recombinant ADAMTS4. 37 Since, ADAMTS4 is able to cleave brevican at the Glu(395)-Ser(396) bond, 32,38 it can be anticipated that ADAMTS5 hydrolyses brevican at least at the same site. Brevican degradation may also be accomplished by other proteases.…”

Section: Discussionmentioning

confidence: 99%

Matrix‐degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas

Held‐Feindt

Paredes

Blömer

et al. 2005

Intl Journal of Cancer

124

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Brain tumors, in particular glioblastomas, have a high morbidity and mortality, mainly due to their invasive nature. A prerequisite for this invasiveness is cell migration based on increased expression of proteases digesting the extracellular matrix. Brevican, an important extracellular proteoglycan that is upregulated in glioblastomas, can be degraded by certain proteases. We demonstrate that in human glioblastomas secretory proteases like ADAMTS4 and ADAMTS5 (aggrecanases 1 and 2; ADAMTS 5 a disintegrin and metalloproteinase with thrombospondin motifs) are expressed on the mRNA and protein levels in considerable amounts. Realtime RT-PCR shows a higher levels of ADAMTS4 and 5 expressions in glioblastomas in situ, compared to cultured human glioblastoma cells. The upregulation of these proteases in vivo by cytokines may explain this difference. In vitro, transforming growth factor-b induces ADAMTS4, but less ADAMTS5, and interleukin1b ADAMTS5, but not ADAMTS4. As demonstrated by immunohistochemistry and confocal microscopy in situ, ADAMTS5 expression is confined to proliferating glioblastoma cells of surgical tumor sections and with lower intensity to astroglial cells in normal brain sections, as opposed to brevican. In vitro, glioblastoma-derived ADAMTS5 degrades recombinant human brevican to several smaller fragments. Our results show that ADAMTS4 and 5 are upregulated on proliferating glioblastoma cells and these proteases may contribute to their invasive potential. ' 2005 Wiley-Liss, Inc.Key words: glioblastoma; invasion; proteases; extracellular matrix; degradation; cytokines High-grade glial tumors (anaplastic astrocytoma and glioblastoma multiforme) are the most frequent brain tumors in adults. 1,2 Despite multimodal therapeutic efforts, the mean survival time is only 9-12 months for glioblastoma multiforme (WHO Grade IV) and 2 years for anaplastic astrocytoma (WHO Grade III). The ability of individual tumor cells to infiltrate brain tissue is the primary reason for this poor prognosis. Individual tumor cells (''guerrilla cells'') can migrate more than 4.0-7.0 cm from the gross tumor into the surrounding normal brain tissue. 3 In part, the migratory and invasive behavior is a consequence of tumor cell interaction with specific components of the extracellular matrix (ECM). Brain ECM components include laminin, collagen IV, tenascin, fibronectin and proteoglycans. 4 The glycosaminoglycan hyaluronic acid (HA) plays a central role in cellular proliferation, differentiation and migration, and may be a key element in tumor spreading. 5 BEHAB (brain enriched hyaluronan binding)/brevican is a recently identified HA binding protein that belongs to the lectican family. 6-9 BEHAB/brevican expression is developmentally regulated in the central nervous system, in particular during periods of glial cell proliferation and migration. 9 Accordingly, BEHAB/brevican is upregulated in the vast majority of surgical glioblastomas, 9-11 and expression levels and proteolytic cleavage of BEHAB/brevican seem to correlate with tumo...

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“…ADAMTS-2, -3, and -14 function as key regulators of collagen fibril assembly [27]. ADAMTS-1 and -4 are capable of cleaving certain matrix proteoglycans such as versican, brevican, and aggrecan [81,113]. ADAMTS-4 also cleaves nonproteoglycan ECM components such as fibromodulin and decorin [55].…”

Section: Metalloproteinases and Their Inhibitorsmentioning

confidence: 99%

The Basic Science of Tendinopathy

Murrell

2008

Clinical Orthopaedics &Amp; Related Research

302

254

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Tendinopathy is a common clinical problem with athletes and in many occupational settings. Tendinopathy can occur in any tendon, often near its insertion or enthesis where there is an area of stress concentration, and is directly related to the volume of repetitive load to which the tendon is exposed. Recent studies indicate tendinopathy is more likely to occur in situations that increase the ''dose'' of load to the tendon enthesis -including increased activity, weight, advancing age, and genetic factors. The cells in tendinopathic tendon are rounder, more numerous, and show evidence of oxidative damage and more apoptosis. These cells also produce a matrix that is thicker and weaker with more water, more immature and cartilage-like matrix proteins, and less organization. There is now evidence of a population of regenerating stem cells within tendon. These studies suggest prevention of tendinopathy should be directed at reducing the volume of repetitive loads to below that which induces oxidative-induced apoptosis and cartilage-like genes. The management strategies might involve agents or cells that induce tendon stem cell proliferation, repair and restoration of matrix integrity.

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Brevican Is Degraded by Matrix Metalloproteinases and Aggrecanase-1 (ADAMTS4) at Different Sites

Cited by 155 publications

References 35 publications

Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon

Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon

Matrix‐degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas

The Basic Science of Tendinopathy

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