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

Julovi, Sohel M.; Yasuda, Tadashi; Shimizu, Makoto; Hiramitsu, Teruko; Nakamura, Takashi

doi:10.1002/art.20004

Cited by 156 publications

(146 citation statements)

References 40 publications

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“…Recently, Julovi et al (34) demonstrated that direct interaction of high molecular mass HA with CD44 inhibited the induction of MMP-1, MMP-3, and MMP-13 by IL-1␤ in articular chondrocytes. Furthermore, Spessotto et al (35) showed that the HA-CD44 engagement directly inhibited the expression of MMP-9 in osteoclasts.…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan oligosaccharide–induced activation of transcription factors in bovine articular chondrocytes

Ohno¹,

Im²,

Knudson³

et al. 2005

Arthritis & Rheumatism

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Objective. To document the activity profile of transcription factors following chondrocyte stimulation with hyaluronan (HA) hexasaccharides (HA 6 ) and to determine the expression of genes whose transcriptional activation is tightly associated with the transcription factors.Methods. Nuclear extracts from bovine articular chondrocytes treated with HA 6 were subjected to transcription factor protein-DNA array analysis. Electrophoretic mobility shift assay (EMSA) analyses were performed to confirm the results of protein-DNA array. The gene expressions of matrix metalloproteinase 3 (MMP-3), type II collagen, and cartilage oligomeric matrix protein (COMP) were examined by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), and protease activity was assessed by casein zymography.Results. In the protein-DNA array analysis, 12 transcription factors were up-regulated and 2 transcription factors were down-regulated in the chondrocytes treated with HA 6 . The transcription factors retinoic acid receptor (RAR), retinoid X receptor (RXR), and Sp-1 exhibited >2-fold increased activity by HA 6 treatment, as confirmed by EMSA. RT-PCR analysis showed that the expression levels of MMP-3, type II collagen, and COMP messenger RNA, which are tightly associated with the activation of RAR, RXR, or Sp-1, were upregulated by treatment with HA 6 . Addition of high molecular mass HA after HA 6 treatment resulted in abrogation of the MMP-3 induction. Conclusion.These results suggest that HA 6 increase the activity of multiple transcription factors in chondrocytes and signal the enhanced expression of key genes involved in cartilage-matrix remodeling and turnover. The data also demonstrate that high molecular mass HA has a potential to suppress the signaling activated by HA 6 .The glycosaminoglycan hyaluronan (HA) is a critical component of the extracellular matrix of articular cartilage. HA serves as a scaffold for the aggregation of cartilage proteoglycan (1) and, in this manner, forms a continuum of structure throughout the extracellular matrix. In addition, we have shown that HA facilitates the anchorage of these proteoglycan aggregates to the chondrocyte cell surface via its interaction with the membrane HA receptor CD44 (2-4). Thus, it is, in part, the interaction of chondrocytes directly with HA that constitutes the cell-matrix interaction that serves to regulate many aspects of chondrocyte metabolism (5). We have shown previously that one method of interference with the cell-matrix interactions of chondrocytes is through the use of excess small HA oligosaccharides, such as HA hexasaccharides (HA 6 ) (2,4,6). HA 6 compete with high molecular mass HA for CD44 binding; yet, they are too small in size to interfere with HA aggrecan or HA-link protein interactions (1,7,8).The consequences of this loss of cell-matrix interactions can be dramatic. In a previous study, we demonstrated that the addition of small HA oligosaccharides to human or bovine articular cartilage slices resulted in the apparent activation o...

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Section: Discussionmentioning

confidence: 99%

Hyaluronan oligosaccharide–induced activation of transcription factors in bovine articular chondrocytes

Ohno¹,

Im²,

Knudson³

et al. 2005

Arthritis & Rheumatism

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“…Although the inhibitory mechanism of HA is not totally elucidated, HA has been shown to suppress NO production by HBFN-f-stimulated RA chondrocytes through down-regulation of nuclear factor-κB (NF-κB) (39). HA associates with several cell surface proteins such as CD44 (3) and intercellular adhesion molecule-1 (ICAM-1) (7), which are constitutively expressed in chondrocytes (5,14). There is an increasing body of evidence that HA action is mediated through its receptors (7,13,14,36).…”

Section: Reagentsmentioning

confidence: 99%

“…HA associates with several cell surface proteins such as CD44 (3) and intercellular adhesion molecule-1 (ICAM-1) (7), which are constitutively expressed in chondrocytes (5,14). There is an increasing body of evidence that HA action is mediated through its receptors (7,13,14,36). Exogenous FN-fs can penetrate articular cartilage and accumulate around chondrocytes (15).…”

Section: Reagentsmentioning

confidence: 99%

“…These results indicate that HBFN-f acts at least partially via interaction with CD44 in RA and OA chondrocytes. We have already shown that exogenous HA penetrates cartilage and binds chondrocytes via CD44 (14). Thus, blocking experiments with anti-CD44 antibody was conducted to investigate whether the inhibitory mechanism of HA involves CD44 in OA and RA cartilage explant cultures stimulated with HBFN-f (Fig.…”

Section: Correlation Of Cd44 Levels With Hbfn-f-stimulated No Productmentioning

confidence: 99%

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Comparison of hyaluronan effects among normal, osteoarthritis, and rheumatoid arthritis cartilages stimulated with fibronectin fragment

Yasuda

2010

Biomed. Res.

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High molecular weight hyaluronan (HA) is widely used in the treatment of osteoarthritis (OA) and rheumatoid arthritis (RA) by intra-articular injection. However, comparative studies of HA actions on catalytically activated cartilages in different pathologic conditions have rarely been investigated. This study was aimed to compare the inhibitory effects of HA on nitric oxide (NO) production by COOH-terminal heparin-binding fibronectin fragment (HBFN-f) between normal and diseased cartilages. When articular cartilage explants from normal, OA, or RA joints were incubated with HBFN-f, the RA and OA cartilages produced higher levels of NO compared with normal cartilage. Pretreatment with 2700 kDa HA resulted in significant suppression of HBFN-f-stimulated NO production in OA and RA cartilages. While CD44 was up-regulated in OA and RA cartilages, anti-CD44 antibody reversed HA inhibition of HBFN-f action in those cartilages. The present results clearly demonstrated that HA blocked HBFN-f actions in OA and RA cartilages through interaction with CD44. HA, which targets CD44 highly expressed on OA and RA chondrocytes, could suppress catabolic actions by fibronectin fragments like HBFN-f in diseased cartilage.Fibronectin (FN) is a component of normal cartilage matrix. FN consists predominantly of three types of homologous repeating segments (designated I, II, and III). While FN is encoded by a single gene, significant protein heterogeneity results from alternative RNA splicing at three sites, termed Extra type III Domain A (ED-A), Extra type III Domain B (ED-B), and the variable (V) region. The V region is also referred to as the connecting segment between III14-15 (IIICS). There are 10 principal isoforms predicted by RNA splicing patterns, each of which contains amino (NH 2 )-terminal heparin-, gelatin-, cell-and carboxyl (COOH)-terminal heparinbinding domains. Elevated levels of FN are found in osteoarthritic cartilage (12, 21) and in both synovial fluid and plasma of osteoarthritis (OA) and rheumatoid arthritis (RA) (29,34). FN is readily degraded into fragments by proteinases. In OA and RA, activation of extracellular proteolysis may lead to the fragmentation of FN. Indeed, increased levels of 30-200 kDa fibronectin fragments (FN-fs) are found in cartilage and synovial fluid from patients with OA and RA (9, 34). Native FN has no catabolic effect on cartilage. Once FN is fragmented, those proteolytic fragments acquire catalytic activities whereby increased FN-fs are thought to cause cartilage destruction in OA and RA (35). Of FN-fs, the fragments with the central cell-, NH 2 -terminal heparin-and NH 2 -terminal gelatin-binding domains have been extensively investigated. Those FN-fs can stimulate proteoglycan breakdown in cultured articular cartilage explants (8). We have recently found that another FN-f, 40 kDa COOH-terminal heparin-binding fragment containing both the III12-14 and IIICS domains (HBFN-f), enhances type II collagen cleavage by collagenase in association with enhanced production

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“…Recent studies indicate that HA acts through interaction with its cell surface receptors. HA suppresses proinflammatory cytokine-stimulated production of matrix metalloproteinases (MMPs) via CD44 (Shimizu et al 2003) and ICAM-1 (Hiramitsu et al 2006) in RA synovial fibroblasts and via CD44 in OA articular chondrocytes (Julovi et al 2004). Whereas proinflammatory cytokines activate some specific intracellular signaling pathways including mitogenactivated protein kinases (MAPKs) and nuclear factor (NF)-κ B, the receptor-HA binding could result in alteration in such signaling cascades because HA inhibits interleukin (IL)-1β -induced activation of p38 MAPK and NF-κ B via ICAM-1 (Hiramitsu et al 2006).…”

mentioning

confidence: 99%

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

Cited by 156 publications

References 40 publications

Hyaluronan oligosaccharide–induced activation of transcription factors in bovine articular chondrocytes

Hyaluronan oligosaccharide–induced activation of transcription factors in bovine articular chondrocytes

Comparison of hyaluronan effects among normal, osteoarthritis, and rheumatoid arthritis cartilages stimulated with fibronectin fragment

Hyaluronan Inhibits Prostaglandin E2 Production via CD44 in U937 Human Macrophages

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