Association of Proteoglycan Degradation with Catabolic Cytokine and Stromelysin Release from Cartilage Cultured with Fibronectin Fragments

Homandberg, Gene A.; Hui, Francis

doi:10.1006/abbi.1996.0461

Cited by 88 publications

(110 citation statements)

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“…In periodontal disease, PDL cell function is compromised as bacterial proteases destroy the integrity of the ECM and release fragmented adhesion molecules, including fibronectin fragments that induce apoptosis, into the inflammatory milieu. In addition, the degraded matrix molecules, like those from fibronectin and hyaluronan, may stimulate the resident cells around the sites of inflammation to produce proinflammatory cytokines and nitric oxide (6,28,30,31,34,56,67,76).…”

mentioning

confidence: 99%

Porphyromonas gingivalis, Gamma Interferon, and a Proapoptotic Fibronectin Matrix Form a Synergistic Trio That Induces c-Jun N-Terminal Kinase 1-Mediated Nitric Oxide Generation and Cell Death

Ghosh¹,

Park²,

Fenno

et al. 2008

Infect Immun

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During infection and inflammation, bacterial and inflammatory proteases break down extracellular matrices into macromolecular fragments. Fibronectin fragments are associated with disease severity in arthritis and periodontitis. The mechanisms by which these fragments contribute to disease pathogenesis are unclear. One likely mechanism is that fibronectin fragments induce apoptosis of resident cells, which can be further modulated by nitric oxide. Nitric oxide levels are increased at inflammatory sites in periodontitis patients. The aim of this study was to examine whether a proapoptotic fibronectin matrix (AFn) exerts its action by inducing nitric oxide and whether priming by bacterial and inflammatory components exacerbates this mechanism. Our data demonstrate that AFn increased the levels of nitric oxide and inducible nitric oxide synthase (iNOS) dose and time dependently in periodontal ligament (PDL) cells. These effects and apoptosis were inhibited by iNOS suppression and enhanced by iNOS overexpression. Nitric oxide and iNOS induction were paralleled by increased c-Jun N-terminal kinase 1 (JNK-1) phosphorylation. JNK-1 overexpression enhanced the expression of nitric oxide and iNOS, whereas inhibiting JNK-1 by small interfering RNA or a kinase mutant reversed these findings. Priming PDL cells with Porphyromonas gingivalis, its lipopolysaccharide (LPS), or gamma interferon (IFN-␥) further increased nitric oxide levels and apoptosis. Escherichia coli and Streptococcus mutans induced lesser effects. Gingival fibroblasts and neutrophils responded to a lesser degree to these stimuli, whereas keratinocytes were resistant to apoptosis. Thus, proapoptotic matrices trigger nitric oxide release via JNK-1, promoting further apoptosis in host cells. LPS and IFN-␥ accentuate this mechanism, suggesting that during inflammation, the affected matrices and bacterial and inflammatory components combined exert a greater pathogenic effect on host cells.

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confidence: 99%

Porphyromonas gingivalis, Gamma Interferon, and a Proapoptotic Fibronectin Matrix Form a Synergistic Trio That Induces c-Jun N-Terminal Kinase 1-Mediated Nitric Oxide Generation and Cell Death

Ghosh¹,

Park²,

Fenno

et al. 2008

Infect Immun

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“…It elevates matrix metalloproteinase, production (2), enhances rates of proteoglycan loss, and suppresses proteoglycan synthesis in cartilage explant culture (1). FN-f also increases the levels of tumor necrosis factor-␣, interleukin-1␤ (IL-1␤), and IL-1␣ in cultured human articular cartilage (3). The pathophysiological significance of these FN-f activities is supported by in vivo studies where injection of FN-f into rabbit knee joints caused depletion of cartilage proteoglycan (4).…”

mentioning

confidence: 99%

Focal Adhesion Kinase and Mitogen-activated Protein Kinases Are Involved in Chondrocyte Activation by the 29-kDa Amino-terminal Fibronectin Fragment

Gemba

Valbracht

Alsalameh

et al. 2002

Journal of Biological Chemistry

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“…The early catabolic phase of damage is also associated with enhanced release of catabolic cytokines as described (65,69). Fn-fs added to human knee cartilage explants caused a peak of release of TNF-alpha and IL-1-beta that decreased after a few days as shown in Figure 2C.…”

Section: High Concentrations Of Fn-fs Enhance Release Of Catabolic Cymentioning

confidence: 98%

“…By these methods, collagenolytic (MMP-1), gelatinolytic (MMP-2, MMP-9) and stromelysin-1(MMP-3)-like activities are increased by at least several-fold (56,63,64). Up-regulation of protein levels of MMP-3 has been confirmed in both bovine (63,64) and human knee explants (65). At least two MMPs are up-regulated at the mRNA level in a concentration-dependent fashion, MMP-3 and MMP-9 (64).…”

Section: Fn-fs Enhance Levels Of Proteinasesmentioning

confidence: 99%

“…Therefore, throughout this review the term Fn-f will be used generically. The typical Fn-fs studied by us are generated by sequential cathepsin D and thrombin digestion of human plasma Fn (56,60,61) and are active on bovine (56), human knee (62,65), rabbit and rat cartilage explant cultures (unpublished). Similar cathepsin D and thrombin generated Fn-fs from rabbit plasma Fn, bovine plasma Fn, rat plasma Fn or guinea pig plasma Fn are equally active on bovine cartilage (unpublished).…”

Section: Fn-fs Enhance Loss Of Pg From Cartilage Explantsmentioning

confidence: 99%

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Potential regulation of cartilage metabolism in osteoarthritis by fibronectin fragments

Homandberg¹

1999

Front Biosci

111

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Association of Proteoglycan Degradation with Catabolic Cytokine and Stromelysin Release from Cartilage Cultured with Fibronectin Fragments

Cited by 88 publications

References 0 publications

Porphyromonas gingivalis, Gamma Interferon, and a Proapoptotic Fibronectin Matrix Form a Synergistic Trio That Induces c-Jun N-Terminal Kinase 1-Mediated Nitric Oxide Generation and Cell Death

Porphyromonas gingivalis, Gamma Interferon, and a Proapoptotic Fibronectin Matrix Form a Synergistic Trio That Induces c-Jun N-Terminal Kinase 1-Mediated Nitric Oxide Generation and Cell Death

Focal Adhesion Kinase and Mitogen-activated Protein Kinases Are Involved in Chondrocyte Activation by the 29-kDa Amino-terminal Fibronectin Fragment

Potential regulation of cartilage metabolism in osteoarthritis by fibronectin fragments

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