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Article: High binding capacity of cyclophilin B to chondrocyte heparan sulfate proteoglycans and its release from the cell surface by matrix metalloproteinases: Possible role as a proinflammatory mediator in arthritis

TitleHigh binding capacity of cyclophilin B to chondrocyte heparan sulfate proteoglycans and its release from the cell surface by matrix metalloproteinases: Possible role as a proinflammatory mediator in arthritis
Authors
Issue Date2003
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0004-3591/
Citation
Arthritis And Rheumatism, 2003, v. 48 n. 8, p. 2197-2206 How to Cite?
AbstractObjective. To study cyclophilin B, a protein newly identified as a secretion product of cultured chondrocytes, in the context of chondrocyte pathobiology. Methods. Cyclophilin B was purified by sequential chromatographic processing of the secretion medium of cultured guinea pig chondrocytes. Its presence both at the surface of chondrocyte monolayers and in cartilage was demonstrated by immunohistochemistry. Binding sites at the surface of chondrocytes were characterized by Scatchard plot analysis using 125I-labeled cyclophilin B, and by glycosidase treatments. The release of cyclophilin B from chondrocytes by activated matrix metalloproteinases (MMPs) was studied by Western blot analysis. Results. Cyclophilin B was present at the surface of cultured chondrocytes and within cartilage, both in cells and in the extracellular matrix, with a particularly intense staining in the superficial layer. It was secreted constitutively by chondrocytes and cartilage explants. Its secretion was enhanced after treatment with its pharmacologic binding partner, cyclosporin A (CSA). Experiments with 125I-labeled cyclophilin B demonstrated the presence of high-capacity, low-affinity, NaCl-sensitive binding sites at the surface of chondrocytes. Cell-bound cyclophilin B could be released by heparinase treatment, demonstrating binding to pericellular heparan sulfate proteoglycans (HSPGs). Chondroitinase or keratanase treatments had no effect. MMPs 1, 2, 3, 9, and 13 released intact cyclophilin B from the cell surface, probably by cleavage of HSPGs. This effect was reversed by the broad-spectrum MMP inhibitor, marimastat. Conclusion. Cyclophilin B is a secreted CSA-binding protein involved in inflammatory events. It can induce chemotaxis in human neutrophils and T lymphocytes. The finding that cyclophilin B is an intrinsic component of cartilage and that it can be released by MMPs suggests that it has a role in the pathogenesis of arthritic diseases, even more so since its signaling receptor is present within the inflamed joint both on T cells and in the rheumatoid synovium.
Persistent Identifierhttp://hdl.handle.net/10722/80257
ISSN
2015 Impact Factor: 8.955
2015 SCImago Journal Rankings: 3.206
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorDe Ceuninck, Fen_HK
dc.contributor.authorAllain, Fen_HK
dc.contributor.authorCaliez, Aen_HK
dc.contributor.authorSpik, Gen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.date.accessioned2010-09-06T08:04:17Z-
dc.date.available2010-09-06T08:04:17Z-
dc.date.issued2003en_HK
dc.identifier.citationArthritis And Rheumatism, 2003, v. 48 n. 8, p. 2197-2206en_HK
dc.identifier.issn0004-3591en_HK
dc.identifier.urihttp://hdl.handle.net/10722/80257-
dc.description.abstractObjective. To study cyclophilin B, a protein newly identified as a secretion product of cultured chondrocytes, in the context of chondrocyte pathobiology. Methods. Cyclophilin B was purified by sequential chromatographic processing of the secretion medium of cultured guinea pig chondrocytes. Its presence both at the surface of chondrocyte monolayers and in cartilage was demonstrated by immunohistochemistry. Binding sites at the surface of chondrocytes were characterized by Scatchard plot analysis using 125I-labeled cyclophilin B, and by glycosidase treatments. The release of cyclophilin B from chondrocytes by activated matrix metalloproteinases (MMPs) was studied by Western blot analysis. Results. Cyclophilin B was present at the surface of cultured chondrocytes and within cartilage, both in cells and in the extracellular matrix, with a particularly intense staining in the superficial layer. It was secreted constitutively by chondrocytes and cartilage explants. Its secretion was enhanced after treatment with its pharmacologic binding partner, cyclosporin A (CSA). Experiments with 125I-labeled cyclophilin B demonstrated the presence of high-capacity, low-affinity, NaCl-sensitive binding sites at the surface of chondrocytes. Cell-bound cyclophilin B could be released by heparinase treatment, demonstrating binding to pericellular heparan sulfate proteoglycans (HSPGs). Chondroitinase or keratanase treatments had no effect. MMPs 1, 2, 3, 9, and 13 released intact cyclophilin B from the cell surface, probably by cleavage of HSPGs. This effect was reversed by the broad-spectrum MMP inhibitor, marimastat. Conclusion. Cyclophilin B is a secreted CSA-binding protein involved in inflammatory events. It can induce chemotaxis in human neutrophils and T lymphocytes. The finding that cyclophilin B is an intrinsic component of cartilage and that it can be released by MMPs suggests that it has a role in the pathogenesis of arthritic diseases, even more so since its signaling receptor is present within the inflamed joint both on T cells and in the rheumatoid synovium.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0004-3591/en_HK
dc.relation.ispartofArthritis and Rheumatismen_HK
dc.titleHigh binding capacity of cyclophilin B to chondrocyte heparan sulfate proteoglycans and its release from the cell surface by matrix metalloproteinases: Possible role as a proinflammatory mediator in arthritisen_HK
dc.typeArticleen_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/art.11099en_HK
dc.identifier.pmid12905473en_HK
dc.identifier.scopuseid_2-s2.0-0043074679en_HK
dc.identifier.hkuros95759en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0043074679&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume48en_HK
dc.identifier.issue8en_HK
dc.identifier.spage2197en_HK
dc.identifier.epage2206en_HK
dc.identifier.isiWOS:000184585000015-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridDe Ceuninck, F=6602162018en_HK
dc.identifier.scopusauthoridAllain, F=6603685404en_HK
dc.identifier.scopusauthoridCaliez, A=9747580500en_HK
dc.identifier.scopusauthoridSpik, G=7006843431en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK

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