Changes in immunolocalisation of β-dystroglycan and specific degradative enzymes in the osteoarthritic synovium

Wimsey, Simon; Lien, Chun Fu; Sharma, Sanjay; Brennan, Peter A.; Roach, Helmtrud I.; Harper, GD; Górecki, Dariusz C.

doi:10.1016/j.joca.2006.04.012

Cited by 16 publications

(16 citation statements)

References 29 publications

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“…Kahn et al (2000) demonstrated increased ADAMTS-4 mRNA expression in HUVECs differentiating in response to growth factors including VEGF, and detected intense ADAMTS-4 mRNA expression in vascular endothelium in areas of inflammation. However, Wimsey et al (2006) failed to detect immunohistochemical staining of ADAMTS-4 in osteoarthritic synovium. Our data clearly demonstrate the presence of ADAMTS-4 mRNA in isolated HUVECs and HuDMECs, but the quantitative relationship between AD-AMTS-4 mRNA and protein is not known.…”

Section: Discussionmentioning

confidence: 91%

“…(2000) demonstrated increased ADAMTS‐4 mRNA expression in HUVECs differentiating in response to growth factors including VEGF, and detected intense ADAMTS‐4 mRNA expression in vascular endothelium in areas of inflammation. However, Wimsey et al. (2006) failed to detect immunohistochemical staining of ADAMTS‐4 in osteoarthritic synovium.…”

Section: Discussionmentioning

confidence: 93%

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Anti‐angiogenic properties of ADAMTS‐4 in vitro

Hsu

Staton

Cross

et al. 2012

Int J Experimental Path

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Angiogenesis is an indispensable mechanism in development and in many pathologies, including cancer, synovitis and aberrant wound healing. Many angiogenic stimulators and inhibitors have been investigated, and some have progressed to the clinic. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a group of multifunctional proteinases. ADAMTS-1 and ADAMTS-8 have been reported to be anti-angiogenic. Here, we provide evidence that ADAMTS-4, like ADAMTS-1, is expressed by endothelial cells and binds to vascular endothelial groth factor (VEGF). Moreover, ADAMTS-4 inhibited human dermal microvascular endothelial cells (HuDMEC) VEGF-stimulated VEGF receptor (R) R2 phosphorylation, differentiation and migration, suggesting that ADAMTS-4 may be a novel anti-angiogenic molecule.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 93%

Anti‐angiogenic properties of ADAMTS‐4 in vitro

Hsu

Staton

Cross

et al. 2012

Int J Experimental Path

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“…MMP-13 and aggrecanases are over-expressed in the synovial space in many cases of human osteoarthritis (Senolt et al, 2006;Wimsey et al, 2006;Takaishi et al, 2008). Understanding basic signaling pathways of MMP-13 induction may improve therapeutic strategies for chondroprotective therapy.…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase-13 expression in IL-1β-treated chondrocytes by activation of the p38 MAPK/c-Fos/AP-1 and JAK/STAT pathways

Lim

Kim

2011

Arch. Pharm. Res.

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Matrix metalloproteinase-13 (MMP-13, mammalian collagenase) degrades the cartilage matrix in pathological conditions such as osteoarthritis. Here, to establish the signaling pathway to MMP-13 induction, effects of mitogen-activated protein kinase (MAPK) pathway and the possibility of some other signaling pathways involved are investigated in interleukin-1β (IL-1β)-treated human chondrosarcoma cell line, SW1353 cells. IL-1β (10 ng/mL) treatment induced MMP-13 in SW1353 cells, with concomitant activation of nuclear factor-κB, activator protein-1 (AP-1) and MAPKs, including extracellular signal-regulated protein kinase, p38 MAPK and c-Jun N-terminal kinase. Among these MAPKs, only p38 MAPK inhibitor (SB203580) blocked MMP-13 induction and AP-1 activation in IL-1β-treated SW1353 cells. SB203580 also inhibited c-Fos translocation to the nucleus (but not c-Jun). Importantly, IL-1β treatment induced Janus kinase 2 (JAK2) and signal transducer and activator of transcription 1/2 (STAT1/2) activation. The JAK2 inhibitor (AG490) blocked STAT1/2 activation as well as MMP-13 induction in IL-1β-treated SW1353 cells. STAT1/2 siRNA transfection also reduced MMP-13 expression levels. Thus, from the present study, it is concluded that p38 MAPK/c-Fos/AP-1 and JAK2/STAT1/2 are involved in MMP-13 induction of IL-1β-treated human chondrocytes, SW1353 cells. Blocking these signaling pathways may have chondroprotective effects in cartilage degeneration.

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“…The presence of the 30 kDa b-DG fragment has been reported under different pathological conditions of the skeletal muscle, such as Duchenne muscular dystrophy, Fukuyama-type congenital dystrophy and sarcoglycanopathy (12). The 30 kDa b-DG fragment was also detected in tissues subjected to ischemic injury (13,14) and in joint tissues from patients affected by osteoarthritis (15); finally, b-DG degradation was also discovered in some forms of epithelial cancerous cells (16). In any case, the 30 kDa b-DG fragment lacks all or part of the b-DG ectodomain, as it can be detected using the monoclonal antibody 43DAG directed against the C-terminus of b-DG.…”

Section: Introductionmentioning

confidence: 96%

Enzymatic processing of β‐dystroglycan recombinant ectodomain by MMP‐9: Identification of the main cleavage site

et al. 2009

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SummaryDystroglycan (DG) is a membrane receptor belonging to the complex of glycoproteins associated to dystrophin. DG is formed by two subunits, a-DG, a highly glycosylated extracellular matrix protein, and b-DG, a transmembrane protein. The two DG subunits interact through the C-terminal domain of a-DG and the N-terminal extracellular domain of b-DG in a noncovalent way. Such interaction is crucial to maintain the integrity of the plasma membrane. In some pathological conditions, the interaction between the two DG subunits may be disrupted by the proteolytic activity of gelatinases (i.e. MMP-9 and/or MMP-2) that removes a portion or the whole b-DG ectodomain producing a 30 kDa truncated form of b-DG. However, the molecular mechanism underlying this event is still unknown. In this study, we carried out proteolysis of the recombinant extracellular domain of b-DG, b-DG(654-750) with human MMP-9, characterizing the catalytic parameters of its cleavage. Furthermore, using a combined approach based on SDS-PAGE, MALDI-TOF and HPLC-ESI-IT mass spectrometry, we were able to identify one main MMP-9 cleavage site that is localized between the amino acids His-715 and Leu-716 of b-DG, and we analysed the proteolytic fragments of b-DG(654-750) produced by MMP-9 enzymatic activity.

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Changes in immunolocalisation of β-dystroglycan and specific degradative enzymes in the osteoarthritic synovium

Cited by 16 publications

References 29 publications

Anti‐angiogenic properties of ADAMTS‐4 in vitro

Anti‐angiogenic properties of ADAMTS‐4 in vitro

Matrix metalloproteinase-13 expression in IL-1β-treated chondrocytes by activation of the p38 MAPK/c-Fos/AP-1 and JAK/STAT pathways

Enzymatic processing of β‐dystroglycan recombinant ectodomain by MMP‐9: Identification of the main cleavage site

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