The role of oncostatin M in animal and human connective tissue collagen turnover and its localization within the rheumatoid joint

Cawston, Timothy E.; Curry, Valerie; Summers, Charlotte; Clark, Ian M.; Riley, Graham P.; Life, P. F.; Spaull, J. R.; Goldring, Mary B.; Koshy, P. J. T.; Rowan, Andrew D.; Shingleton, W. D.

doi:10.1002/1529-0131(199810)41:10<1760::aid-art8>3.3.co;2-d

Cited by 57 publications

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“…Since the aggrecanases ADAM-TS4 and ADAM-TS5 contain the typical furin recognition motif (9,10) and ADAM-TS4 can be processed by furin (34), we investigated the effect on proteoglycan release of adding the furin inhibitor Dec-RVKR-CH 2 Cl to stimulated cartilage. A marked release of proteoglycan was seen from cartilage stimulated for 3 days with IL-1␣ (1 ng/ml) in combination with OSM (10 ng/ml), as previously reported (15,36). This release was partially blocked following inclusion of Dec-RVKR-CH 2 Cl at 100 M (Figure 6), suggesting that furin is involved in processing enzymes that lead to the breakdown of cartilage proteoglycan.…”

Section: Resultssupporting

confidence: 80%

“…After 14 days in explant culture, this combination of cytokines resulted in an increase in the synthesis of procollagenases and a reproducible release of collagen and proteoglycan fragments (15,36). Moreover, most of the proteoglycan was degraded by day 3 of the culture while the collagen release occurred later, with Ͼ90% collagen release by day 14.…”

Section: Discussionmentioning

confidence: 99%

“…The production of MMPs and inhibitors is mediated by a variety of cytokines and growth factors. Proinflammatory cytokines, such as tumor necrosis factor ␣ (TNF␣), IL-1␣, and oncostatin M (OSM), have been shown to stimulate chondrocytes and synovial cells to produce MMPs, and increased levels of these cytokines are present in the arthritic joint (15,16).…”

mentioning

confidence: 99%

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Inhibition of furin‐like enzymes blocks interleukin‐1α/oncostatin M–stimulated cartilage degradation

Milner¹,

Rowan²,

Sf³

et al. 2003

Arthritis & Rheumatism

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Objective. To investigate the role of furin-like enzymes in the proteolytic cascades leading to cartilage breakdown and to examine which collagenase(s) contribute to collagen degradation.Methods. Bovine nasal cartilage was stimulated to resorb with the addition of interleukin-1␣ (IL-1␣)/ oncostatin M (OSM) in the presence or absence of a furin inhibitor, Dec-RVKR-CH 2 Cl, or selective matrix metalloproteinase 1 (MMP-1) inhibitors. Collagen and proteoglycan levels were determined by assay of hydroxyproline and sulfated glycosaminoglycan, respectively. Collagenase and gelatinase activity were measured using 3 H-acetylated collagen and gelatin zymography, respectively.Results. The addition of Dec-RVKR-CH 2 Cl to stimulated cartilage reduced the release of collagen fragments and the levels of active collagenase and MMP-2, suggesting that furin-like enzymes are involved in the cascades leading to activation of procollagenases. At MMP inhibitor concentrations that selectively inhibit MMP-1, no inhibition of collagen release was observed, but increasing the concentration to the 50% inhibition concentration for MMP-13 resulted in a 50% blockage of collagen release. The addition of Dec-RVKR-CH 2 Cl to resorbing cartilage also partially blocked proteoglycan release, thus demonstrating a role for furin-activated enzymes in the pathways leading to proteoglycan degradation. Conclusion.Furin-like enzymes are involved in cascades leading to activation of procollagenases and degradation of collagen. MMP-13, which can be activated by furin-processed membrane-type 1 MMP-1, appears to be a major collagenase involved in collagen degradation induced by IL-1␣/OSM. Furin-like enzymes also appear to play a role in the pathways leading to proteoglycan degradation. These findings are of importance when considering proteinase inhibition as a target for therapeutic intervention in arthritic diseases.

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Section: Resultssupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

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Inhibition of furin‐like enzymes blocks interleukin‐1α/oncostatin M–stimulated cartilage degradation

Milner¹,

Rowan²,

Sf³

et al. 2003

Arthritis & Rheumatism

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“…MMP secretion by peripheral fibroblasts would potentially facilitate cell recruitment, granuloma expansion and minimize structural isolation of the granuloma by collagen deposition, a role traditionally attributed to the fibroblast in TB [12,13]. The potential for fibroblasts to modulate inflammation is well described in rheumatoid arthritis where they orchestrate and perpetuate a chronic inflammatory response by a combination of matrix degradation and cell recruitment [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…38: 1321-1330 Immunity to infection in TB [12,13]. The potential for fibroblasts to modulate inflammation is well described in rheumatoid arthritis where they orchestrate and perpetuate a chronic inflammatory response by a combination of matrix degradation and cell recruitment [14][15][16]. Oncostatin M (OSM) is a key factor in mediating matrix degradation in extrapulmonary sites [17] where it synergizes with pro-inflammatory cytokines to induce MMP.…”

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confidence: 99%

Monocyte‐dependent oncostatin M and TNF‐α synergize to stimulate unopposed matrix metalloproteinase‐1/3 secretion from human lung fibroblasts in tuberculosis

2008

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Leukocyte-derived matrix metalloproteinases (MMP) are implicated in the tissue destruction characteristic of tuberculosis (TB). The contribution of lung stromal cells to MMP activity in TB is unknown. Oncostatin M (OSM) is an important stimulus to extrapulmonary stromal MMP induction, but its role in regulation of pulmonary MMP secretion or pathophysiology of TB is unknown. We investigated OSM secretion from Mycobacterium tuberculosis (Mtb)-infected human monocytes/macrophages and the networking effects of such OSM on lung fibroblast MMP secretion. Mtb increased monocyte OSM secretion dose dependently in vitro. In vivo tuberculous granulomas immunostained positively for OSM. Further, conditioned media from Mtb-infected monocytes (CoMTb) induced monocyte OSM secretion (670 AE 55 versus 166 AE 14 pg/mL in controls), implicating an autocrine loop. Mtbinduced OSM secretion was prostaglandin (PG) sensitive, and required activation of surface G-protein coupled receptors. OSM induction was ERK MAP kinase dependent, p38-requiring but JNK-independent. OSM synergized with TNF-a, a key cytokine in TB granuloma formation, to stimulate pulmonary fibroblast MMP-1/-3 secretion, while suppressing secretion of tissue inhibitors of metalloproteinases-1/-2. In summary, Mtb infection of monocytes results in PG-dependent OSM secretion, which synergizes with TNF-a to drive functionally unopposed fibroblast MMP-1/-3 secretion, demonstrating a previously unrecognized role for OSM in TB.Key words: Human Á Inflammation Á Monocytes/macrophages Á Stromal cells Introduction Tuberculosis (TB) remains a major global health problem with over 8 million cases of overt clinical infection, and 2 million deaths annually. The pathological response to Mycobacterium tuberculosis (Mtb) infection is characterised by extensive tissue breakdown including caseous necrosis, and later fibrosis. Tissue destruction in TB requires degradation of matrix proteins including collagen and elastin, and several studies have implicated matrix metalloproteinases (MMP) in pathogenesis [1][2][3]. MMP are a group of 23 related zinc-dependent enzymes that together are capable of degrading all components of the extracellular matrix (ECM) [4]. MMP are inhibited in vivo by the tissue inhibitors of metalloproteinases (TIMP), and in general, overall proteolytic activity is determined by the molar ratio of MMP:TIMP. MMP secretion is induced by inflammatory cytokines, physical stimuli, or directly by some bacterial components [5]. Direct infection of mononuclear cells with Mtb has been shown to induce MMP-9 (gelatinase B), a process that depends in part on 6].In the lung, the principal structural supporting collagen is type I [7,8]. MMP-1 (interstitial collagenase) is the most abundant pulmonary enzyme capable of degrading type I collagen [5]. Several cell types secrete MMP-1 in TB [9,10] but there are no data on the role of fibroblast-derived MMP-1 in TB. However, stimulated fibroblasts are the most potent source of MMP-1 in the lung [11] and may cause type IV collagen and prote...

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Retinoic acid combines with interleukin-1 to promote the degradation of collagen from bovine nasal cartilage: Matrix metalloproteinases-1 and -13 are involved in cartilage collagen breakdown

et al. 2000

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Retinoic acid (RetA) and interleukin-1alpha (IL-1) together can induce a reproducible release of proteoglycan fragments from bovine nasal cartilage in culture. However, release of collagen fragments with either agent alone is often variable. In this study over 70% of the total collagen was released from bovine nasal cartilage in culture by day 14 when RetA and IL-1 were combined. This release was accompanied by the appearance of collagenolytic activity in the culture medium that cleaved collagen specifically at the (1/4)/(3/4) position. Tissue inhibitor of metalloproteinases (TIMP) activity was present at day 7 but low or absent in media from resorbing tissue at day 14. The breakdown of cartilage collagen could be prevented by the addition of BB-94, a specific metalloproteinase inhibitor. These results suggest that RetA promotes the early release of TIMP from the tissue and that IL-1 stimulates pro-collagenase secretion which, when activated, exceeds the local concentration of TIMP. Thus in the later stages of culture collagen destruction occurs. Both MMP-1 and MMP-13 were detected and appear to be involved in IL-1 + RetA induced bovine cartilage destruction. However, for the first time, we also present evidence to suggest that MMP-13 is the predominant collagenase in this system.

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The role of oncostatin M in animal and human connective tissue collagen turnover and its localization within the rheumatoid joint

Cited by 57 publications

References 0 publications

Inhibition of furin‐like enzymes blocks interleukin‐1α/oncostatin M–stimulated cartilage degradation

Inhibition of furin‐like enzymes blocks interleukin‐1α/oncostatin M–stimulated cartilage degradation

Monocyte‐dependent oncostatin M and TNF‐α synergize to stimulate unopposed matrix metalloproteinase‐1/3 secretion from human lung fibroblasts in tuberculosis

Retinoic acid combines with interleukin-1 to promote the degradation of collagen from bovine nasal cartilage: Matrix metalloproteinases-1 and -13 are involved in cartilage collagen breakdown

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