Anti-Fas-induced apoptosis in chondrocytes reduced by hyaluronan: Evidence for CD44 and CD54 (intercellular adhesion molecule 1) involvement

Lisignoli, Gina; Grassi, Francesco; Zini, Nicoletta; Toneguzzi, Stefania; Piacentini, A.; Guidolin, Diego; Bevilacqua, C.; Facchini, Andrea

doi:10.1002/1529-0131(200108)44:8<1800::aid-art317>3.0.co;2-1

Cited by 115 publications

(68 citation statements)

References 35 publications

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“…Treatment with IM7 resulted in a significant reduction of the inhibitory effects of HA on MMP production in IL-1␤-stimulated cartilage (Figures 5 and 7). The interaction between HA and CD44 has been shown to reduce anti-Fas-induced apoptosis of chondrocytes (36), which is further evidence of the direct involvement of CD44 in the mechanism of HA action. Antisense inhibition of chondrocyte CD44 expression results in proteoglycan degradation with NITEGE expression in cartilage (37), indicating that CD44 may be a key player in the maintenance of the cartilage structure.…”

Section: Discussionmentioning

confidence: 65%

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Inhibition of interleukin‐1β‐stimulated production of matrix metalloproteinases by hyaluronan via CD44 in human articular cartilage

Julovi

Yasuda

Shimizu

et al. 2004

Arthritis & Rheumatism

156

123

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Objective. To investigate the mechanism of the inhibitory action of hyaluronan (HA) on interleukin-1␤ (IL-1␤)-stimulated production of matrix metalloproteinases (MMPs) in human articular cartilage.Methods. IL-1␤ was added to normal and osteoarthritic (OA) human articular cartilage in explant culture to stimulate MMP production. Articular cartilage was incubated or preincubated with a clinically used form of 800-kd HA to assess its effect on IL-1␤-induced MMPs. Levels of secreted MMPs 1, 3, and 13 in conditioned media were detected by immunoblotting; intracellular MMP synthesis in chondrocytes was evaluated by immunofluorescence microscopy. Penetration of HA into cartilage tissue and its binding to CD44 were analyzed by fluorescence microscopy using fluoresceinated HA. Blocking experiments with anti-CD44 antibody were performed to investigate the mechanism of action of HA.Results. Treatment and pretreatment with 800-kd HA at 1 mg/ml resulted in significant suppression of IL-1␤-stimulated production of MMPs 1, 3, and 13 in normal and OA cartilage explant culture. Fluorescence histocytochemistry revealed that HA penetrated cartilage tissue and localized in the pericellular matrix around chondrocytes. HA-binding blocking experiments using anti-CD44 antibody demonstrated that the association of HA with chondrocytes was mediated by CD44. Preincubation with anti-CD44 antibody, which suppressed IL-1␤-stimulated MMPs, reversed the inhibitory effect of HA on MMP production that was induced by IL-1␤ in normal and OA cartilage.Conclusion. This study demonstrates that HA effectively inhibits IL-1␤-stimulated production of MMP-1, MMP-3, and MMP-13, which supports the clinical use of HA in the treatment of OA. The action of HA on IL-1␤ may involve direct interaction between HA and CD44 on chondrocytes.Osteoarthritis (OA) is the most prevalent disease of articular joints and is the major cause of disability in the elderly. Pathophysiologic changes occur in OA cartilage due to the excessive expression of cartilagedegrading proteinases, the resultant progressive breakdown of collagen fibers, and the degradation of proteoglycan, mainly aggrecan (1).Matrix metalloproteinases (MMPs) are zinccontaining, calcium-dependent proteinases, which collectively degrade all components of the extracellular matrix. MMPs are considered to be important in the chondrolytic processes that contribute to the degenerative changes in OA cartilage (2-4). Recent studies have identified the messenger RNA (mRNA) for some MMPs, such as MMP-1, in human OA cartilage (4,5), and other investigators have reported specific MMP proteins and collagenasemediated type II collagen degradation products (6,7). There is a consensus that these enzymes play a critical role in intrinsic chondrocyte-mediated degenerative changes of the cartilage matrix in OA. Proinflammatory cytokines such as interleukin-1 (IL-1) strongly stimulate the expression of MMPs by chondrocytes in arthritis (8).Hyaluronan (HA) is a major component of synovial fluid and cartilage matrix, and it play...

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Section: Discussionmentioning

confidence: 65%

“…HA has been shown to be a potent inhibitor of proteoglycan depletion in rabbit articular cartilage (34). In addition, HA can reduce anti-Fas-induced apoptosis of OA chondrocytes (36). Indeed, arthroscopic evaluations of articular cartilage have demonstrated a potential structure-modifying effect of HA in patients with knee OA (42,43).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of interleukin‐1β‐stimulated production of matrix metalloproteinases by hyaluronan via CD44 in human articular cartilage

Julovi

Yasuda

Shimizu

et al. 2004

Arthritis & Rheumatism

156

123

View full text Add to dashboard Cite

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“…These matrices are seen as a gel-like, transparent zone extending by up to one cell diameter away from the plasma membrane (2,10). In cells such as chondrocytes that exhibit large cell-associated matrices, the presence of high molecular mass HA appears to promote quiescence, dampens matrix degradation induced by inflammatory cytokines (12)(13)(14) or fragmented fibronectin (15,16), and inhibits FAS ligandinduced apoptosis (17). We have also recently demonstrated that high molecular mass HA promotes the interaction between CD44 and Smad1, an interaction that appears necessary for optimal presentation of Smad1 to the bone morphologic protein-7 receptor complex (18).…”

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confidence: 99%

Hyaluronan Oligosaccharides Induce Matrix Metalloproteinase 13 via Transcriptional Activation of NFκB and p38 MAP Kinase in Articular Chondrocytes

Ohno

Knudson

et al. 2006

Journal of Biological Chemistry

114

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Hyaluronan exerts a variety of biological effects on cells including changes in cell migration, proliferation, and matrix metabolism. However, the signaling pathways associated with the action of hyaluronan on cells have not been clearly defined. In some cells, signaling is induced by the loss of cell-hyaluronan interactions. The goal of this study was to use hyaluronan oligosaccharides as a molecular tool to explore the effects of changes in cell-hyaluronan interactions and determine the underlying molecular events that become activated. In this study, hyaluronan oligosaccharides induced the loss of extracellular matrix proteoglycan and collagen from cultured slices of normal adult human articular cartilage. This loss was coincident with an increased expression of matrix metalloproteinase (MMP)-13. MMP-13 expression was also induced in articular chondrocytes by hyaluronan (HA) hexasaccharides but not by HA tetrasaccharides nor high molecular weight hyaluronan. MMP-13 promoterreporter constructs in CD44-null COS-7 cells revealed that both CD44-dependent and CD44-independent events mediate the induction of MMP-13 by hyaluronan oligosaccharides. Electromobility gel shift assays demonstrated the activation of chondrocyte NFB by hyaluronan oligosaccharides. NFB activation was also documented in C-28/I2 immortalized human chondrocytes by luciferase promoter assays and phosphorylation of IKK-␣/␤. The link between activation of NFB and MMP-13 induction by HA oligosaccharides was further confirmed through the use of the NFB inhibitor helenalin. Inhibition of MAP kinases also demonstrated the involvement of p38 MAP kinase in the hyaluronan oligosaccharide induction of MMP-13. Our findings suggest that hyaluronan-CD44 interactions affect matrix metabolism via activation of NFB and p38 MAP kinase.In many tissues cell-matrix interactions serve to regulate cellular homeostasis (1, 2). Interference with these associations typically signal cells to initiate matrix repair, cell proliferation, or even cell migration. Such interactions are especially important in tissues such as articular cartilage, a tissue rich in extracellular matrix but with limited vascular access for systemic control of homeostasis. Chondrocytes are thus highly dependent on cell-matrix interactions as a primary means to "sense" changes in the extracellular environment (3). Most investigations in this area focus on cell signaling induced through the interaction of integrin receptors with collagens, fibronectin, laminin, matrilins, etc.(3-7). However, cell-matrix interactions involving hyaluronan (HA), 2 once thought to be predominately structural in nature, are now beginning to receive increasing attention as initiators of cell signaling.HA is a high molecular weight polysaccharide consisting of repeating disaccharide units glucuronic acid and N-acetylglucosamine (8). In cartilage and many other connective tissues, HA serves as a central filamentous scaffold to which proteoglycans such as aggrecan and link protein become bound (9). This complex matrix networ...

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“…Certainly, versican cleavage can help loosen the HA strand network, thereby altering the interaction of HA with adhesive proteins and with cell surface receptors. Indeed, a growing body of evidence suggest that HA can also directly participate in sustaining the vitality of several cell types by binding to HA cell surface receptors, mainly to CD44 (72)(73)(74)(75). This molecular interaction seems also to take part in the control of cumulus survival.…”

Section: Discussionmentioning

confidence: 99%

Cyclic AMP-elevating Agents Promote Cumulus Cell Survival and Hyaluronan Matrix Stability, Thereby Prolonging the Time of Mouse Oocyte Fertilizability

Giacomo

Camaioni

Klinger

et al. 2016

Journal of Biological Chemistry

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Cumulus cells sustain the development and fertilization of the mammalian oocyte. These cells are retained around the oocyte by a hyaluronan-rich extracellular matrix synthesized before ovulation, a process called cumulus cell-oocyte complex (COC) expansion. Hyaluronan release and dispersion of the cumulus cells progressively occur after ovulation, paralleling the decline of oocyte fertilization. We show here that, in mice, postovulatory changes of matrix are temporally correlated to cumulus cell death. Cumulus cell apoptosis and matrix disassembly also occurred in ovulated COCs cultured in vitro. COCs expanded in vitro with FSH or EGF underwent the same changes, whereas those expanded with 8-bromo-adenosine-3,5-cyclic monophosphate (8-Br-cAMP) maintained integrity for a longer time. It is noteworthy that 8-Br-cAMP treatment was also effective on ovulated COCs cultured in vitro, prolonging the vitality of the cumulus cells and the stability of the matrix from a few hours to >2 days. Stimulation of endogenous adenylate cyclase with forskolin or inhibition of phosphodiesterase with rolipram produced similar effects. The treatment with selective cAMP analogues suggests that the effects of cAMP elevation are exerted through an EPAC-independent, PKA type II-dependent signaling pathway, probably acting at the post-transcriptional level. Finally, overnight culture of ovulated COCs with 8-Br-cAMP significantly counteracted the decrease of fertilization rate, doubling the number of fertilized oocytes compared with control conditions. In conclusion, these studies suggest that cAMP-elevating agents prevent cumulus cell senescence and allow them to continue to exert beneficial effects on oocyte and sperm, thereby extending in vitro the time frame of oocyte fertilizability.

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Anti-Fas-induced apoptosis in chondrocytes reduced by hyaluronan: Evidence for CD44 and CD54 (intercellular adhesion molecule 1) involvement

Cited by 115 publications

References 35 publications

Inhibition of interleukin‐1β‐stimulated production of matrix metalloproteinases by hyaluronan via CD44 in human articular cartilage

Inhibition of interleukin‐1β‐stimulated production of matrix metalloproteinases by hyaluronan via CD44 in human articular cartilage

Hyaluronan Oligosaccharides Induce Matrix Metalloproteinase 13 via Transcriptional Activation of NFκB and p38 MAP Kinase in Articular Chondrocytes

Cyclic AMP-elevating Agents Promote Cumulus Cell Survival and Hyaluronan Matrix Stability, Thereby Prolonging the Time of Mouse Oocyte Fertilizability

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