Tumor necrosis factor-related apoptosis-inducing ligand induces apoptosis in human articular chondrocytes in vitro

Pettersen, Ingvild; Figenschau, Yngve; Olsen, Eric; Bakkelund, Wenche Helen; Smedsrød, Bård; Sveinbjørnsson, Baldur

doi:10.1016/s0006-291x(02)00916-6

Cited by 45 publications

(34 citation statements)

References 33 publications

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“…One of the OPG ligands, TRAIL, has also been observed in chondrocytes and synovial tissues from OA joints (18,19,22). Moreover, TRAIL is known to induce chondrocyte apoptosis in vitro (22,23). Our immunohistochemical analysis also indicated that TRAIL was expressed in chondrocytes.…”

Section: Prevention Of Chondrocyte Apoptosis In An Experimental Oa Mosupporting

confidence: 53%

Prevention of cartilage destruction with intraarticular osteoclastogenesis inhibitory factor/osteoprotegerin in a murine model of osteoarthritis

Shimizu¹,

Asou²,

Itoh³

et al. 2007

Arthritis & Rheumatism

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Objective. To investigate the effect of osteoclastogenesis inhibitory factor/osteoprotegerin (OPG) on chondrocytes in the development of osteoarthritis (OA) in vivo.Methods. To determine the role of endogenous OPG in the progression of OA, OA was surgically induced in OPG ؉/؊ mice and their wild-type (WT) littermates. To determine the role of exogenous OPG, knee joints of C57BL/6J mice with surgically induced OA were injected intraarticularly with recombinant human OPG (rHuOPG) or vehicle 5 times a week. All mice were euthanized 4 weeks after OA induction; joints were harvested and evaluated immunohistochemically.Results. Although OA changes were induced in both WT and OPG ؉/؊ mice, the degenerative changes in the articular cartilage were significantly enhanced in OPG ؉/؊ mice. In C57BL/6J mice with surgically induced OA, intraarticular OPG administration protected the articular cartilage from the progression of OA. The Mankin and cartilage destruction scores in OPGtreated animals were ϳ50% of those seen in the control group. Furthermore, OPG administration significantly protected articular cartilage thickness. Findings of the TUNEL assay indicated that rHuOPG prevented chondrocyte apoptosis in joints with surgically induced OA. Results of immunostaining indicated that OPG protein was detected in the synovium and in resident chondrocytes at higher levels in the OPG-treated group than in the control group.Conclusion. These data indicate that endogenous OPG had a protective effect against the cartilage destruction that occurs during OA progression. Furthermore, direct administration of rHuOPG to articular chondrocytes prevented cartilage destruction in an experimental murine model of OA via prevention of chondrocyte apoptosis.

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Section: Prevention Of Chondrocyte Apoptosis In An Experimental Oa Mosupporting

confidence: 53%

Prevention of cartilage destruction with intraarticular osteoclastogenesis inhibitory factor/osteoprotegerin in a murine model of osteoarthritis

Shimizu¹,

Asou²,

Itoh³

et al. 2007

Arthritis & Rheumatism

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“…Subsequent studies tempered that initial optimism somewhat. Although the extracellular portion of human TRAIL (amino acids 114 -281, henceforth referred to as soluble TRAIL) was generally tolerated by normal human cells (Ashkenazi et al, 1999), other formulations were found to be toxic to particular normal cell types (Leverkus et al, 2000;Nitsch et al, 2000;Pettersen et al, 2002). Freshly isolated human hepatocytes displayed substantial sensitivity to His-tagged TRAIL, cross-linked TRAIL formulations and agonistic anti-DR4 and DR5 antibodies (Jo et al, 2000;Mori et al, 2004;Ganten et al, 2006), but survived incubation with soluble TRAIL (Ashkenazi et al, 1999;Lawrence et al, 2001;Ganten et al, 2006).…”

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confidence: 99%

In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs

et al. 2008

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TRAIL/Apo-2L has shown promise as an anti-glioma drug, based on investigations of TRAIL sensitivity in established glioma cell lines, but it is not known how accurately TRAIL signalling pathways of glioma cells in vivo are reproduced in these cell lines in vitro. To replicate as closely as possible the in vivo behaviour of malignant glioma cells, 17 early passage glioma cell lines and 5 freshly resected gliomas were exposed to TRAIL-based agents and/or chemotherapeutic drugs. Normal human hepatocytes and astrocytes and established glioma cell lines were also tested. Cross-linked TRAIL, but not soluble TRAIL, killed both normal cell types and cells from three tumours. Cells from only one glioma were killed by soluble TRAIL, although only inefficiently. High concentrations of cisplatin were lethal to glioma cells, hepatocytes and astrocytes. Isolated combinations of TRAIL and chemotherapy drugs were more toxic to particular gliomas than normal cells, but no combination was generally selective for glioma cells. This study highlights the widespread resistance of glioma cells to TRAIL-based agents, but suggests that a minority of high-grade glioma patients may benefit from particular combinations of TRAIL and chemotherapy drugs. In vitro sensitivity assays may help identify effective drug combinations for individual glioma patients.

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“…Chondrocyte apoptosis can be initiated in vitro by IL-1ß [Singh et al, 2002[Singh et al, , 2003], TNF-· [Fischer et al, 2000;Aizawa et al, 2001;Petterson et al, 2002], NO [Blanco et al, 1995;Kim et al, 2002b], Fas/anti-Fas [Hashimoto et al, 1997;Kühn et al, 2000;Kühn and Lotz, 2001;Sun et al, 2002], compression [Bee et al, 2000], hydrostatic pressure Islam et al, 2002], mechanical injury [D'Lima et al, 2001], impact loading [Chen et al, 2001a] and inhibition of type I IGF receptor [Loesser and Shanker, 2000].…”

Section: Induction Of Chondrocyte Apoptosismentioning

confidence: 99%

Pathophysiological Mechanisms in Osteoarthritis Lead to Novel Therapeutic Strategies

Malemud¹,

Islam²,

Haqqi³

2003

Cells Tissues Organs

175

141

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Osteoarthritis (OA) is a debilitating, progressive disease of diarthrodial joints associated with aging. At the molecular level, OA is characterized by an imbalance between anabolic (i.e. extracellular matrix biosynthesis) and catabolic (i.e. extracellular matrix degradation) pathways in which articular cartilage is the principal site of tissue injury responses. The pathophysiology of OA also involves the synovium in that ‘nonclassical’ inflammatory synovial processes contribute to OA progression. Chondrocytes are critical to the OA process in that the progression of OA can be judged by the vitality of chondrocytes and their ability to resist apoptosis. Growth factors exemplified by insulin-like growth factor-1, its binding proteins and transforming growth factor-β contribute to anabolic pathways including compensatory biosynthesis of extracellular matrix proteins. Catabolic pathways are altered by cytokine genes such as interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) which are upregulated in OA. In addition, IL-1 and TNF-α downregulate extracellular matrix protein biosynthesis while concomitantly upregulating matrix metalloproteinase (MMP) gene expression. When MMPs are activated, cartilage extracellular matrix degradation ensues apparently because levels of endogenous cartilage MMP inhibitors cannot regulate MMP activity. Therapeutic strategies designed to modulate the imbalance between anabolic and catabolic pathways in OA may include neutralizing cytokine activity or MMP gene expression or inhibiting signaling pathways which result in apoptosis dependent on mature caspase activity or mitogen-activated protein kinase (MAPK) activity. MAPK activity appears critical for regulating chondrocyte and synoviocyte apoptosis and MMP genes.

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Tumor necrosis factor-related apoptosis-inducing ligand induces apoptosis in human articular chondrocytes in vitro

Cited by 45 publications

References 33 publications

Prevention of cartilage destruction with intraarticular osteoclastogenesis inhibitory factor/osteoprotegerin in a murine model of osteoarthritis

Prevention of cartilage destruction with intraarticular osteoclastogenesis inhibitory factor/osteoprotegerin in a murine model of osteoarthritis

In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs

Pathophysiological Mechanisms in Osteoarthritis Lead to Novel Therapeutic Strategies

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