Yr Athro Clare Hughes
Senior Lecturer
Ysgol y Biowyddorau
Trosolwyg
Research overview
Research interests include:
- The mechanisms by which ADAMTS-4 & TS-5 ('the aggrecanases' ) are involved in cartilage destruction during the pathogenesis of osteoarthritis. Part of this work has led to the novel discovery of an alternative splice-variant of ADAMTS-4 synthesised in synovial tissue.
- The mechanisms by which glycosaminoglycan sulphation motifs influence the differentiation of mesenchymal stem cells to connective tissue lineages with a particular focus on chondrogenesis.
- The pathogenesis of Kashin Beck Disease an endemic osteoarthropathy in China.
Cyhoeddiad
2023
- Dintwa, L., Hughes, C. E. and Blain, E. J. 2023. Importance of mechanical cues in regulating musculoskeletal circadian clock rhythmicity: implications for articular cartilage. Physiological Reports 11(15), article number: e15780. (10.14814/phy2.15780)
- Bains, K. K., Ashworth, S., Koudouna, E., Young, R. D., Hughes, C. E. and Quantock, A. J. 2023. Chondroitin sulphate/dermatan sulphate proteoglycans: potential regulators of corneal stem/progenitor cell phenotype in vitro. International Journal of Molecular Sciences 24(3), article number: 2095. (10.3390/ijms24032095)
2021
- Mutoji, K. N., Sun, M., Elliott, G., Moreno, I. Y., Hughes, C., Gesteira, T. F. and Coulson-Thomas, V. J. 2021. Extracellular matrix deposition and remodeling after corneal alkali burn in mice. International Journal of Molecular Sciences 22(11), article number: 5708. (10.3390/ijms22115708)
- Allaith, S., Tew, S. R., Hughes, C. E., Clegg, P. D., Canty-Laird, E. G. and Comerford, E. J. 2021. Characterisation of key proteoglycans in the cranial cruciate ligaments (CCLs) from two dog breeds with different predispositions to CCL disease and rupture. The Veterinary Journal 272, article number: 105657. (10.1016/j.tvjl.2021.105657)
- Ashworth, S. et al. 2021. Chondroitin sulfate as a potential modulator of the stem cell niche in cornea. Frontiers in Cell and Developmental Biology 8, article number: 567358. (10.3389/fcell.2020.567358)
2020
- Nandadasa, S. et al. 2020. Vascular dimorphism ensured by regulated proteoglycan dynamics favors rapid umbilical artery closure at birth. eLife 9, article number: e60683. (10.7554/eLife.60683)
2017
- Powell, A. et al. 2017. Do model polymer therapeutics sufficiently diffuse through articular cartilage to be a viable therapeutic route?. Journal of Drug Targeting 25(9-10), pp. 919-926. (10.1080/1061186X.2017.1378660)
2016
- Hayes, A. J., Hughes, C. E., Smith, S. M., Caterson, B., Little, C. B. and Melrose, J. 2016. The CS sulphation motifs 4C3, 7D4, 3B3[-]; and perlecan identify stem cell populations and niches, activated progenitor cells and transitional tissue development in the fetal human elbow. Stem Cells and Development 25(11), pp. 836-847. (10.1089/scd.2016.0054)
- Bascoul-Colombo, C., Garaiova, I., Plummer, S. F., Harwood, J. L., Caterson, B. and Hughes, C. E. 2016. Glucosamine hydrochloride but not chondroitin sulfate prevents cartilage degradation and inflammation induced by interleukin-1α in bovine cartilage explants. Cartilage 7(1), pp. 70-81. (10.1177/1947603515603762)
2015
- Esa, A., Archer, C. W., Caterson, B. and Hughes, C. E. 2015. Investigating the role of Wnt antagonist protein Dkk-1 in the pathogenesis of osteoarthritis [Abstract]. International Journal of Experimental Pathology 96(2), pp. A29-A29. (10.1111/iep.12125)
- Chen, J. et al. 2015. Altered proteolytic activity and expression of mmps and aggrecanases and their inhibitors in Kashin-Beck disease. Journal of Orthopaedic Research 33(1), pp. 47-55. (10.1002/jor.22708)
2014
- Luo, M. et al. 2014. Changes in the metabolism of chondroitin sulfate glycosaminoglycans in articular cartilage from patients with Kashin-Beck disease. Osteoarthritis and Cartilage 22(7), pp. 986-995. (10.1016/j.joca.2014.05.012)
2013
- Wainwright, S. D., Bondeson, J., Caterson, B. and Hughes, C. E. 2013. ADAMTS4_v1 is a splice variant of ADAMTS4 that is expressed as a protein in human synovium and cleaves aggrecan at the interglobular domain. Arthritis & Rheumatism 65(11), pp. 2866-2875. (10.1002/art.38102)
- Shu, C. et al. 2013. The ovine newborn and human foetal intervertebral disc contain perlecan and aggrecan variably substituted with native 7D4 CS sulphation motif: spatiotemporal immunolocalisation and co-distribution with Notch-1 in the human foetal disc. Glycoconjugate Journal 30(7), pp. 717-725. (10.1007/s10719-013-9475-9)
- Guan, F. et al. 2013. Histopathology of chondronecrosis development in knee articular cartilage in a rat model of Kashin-Beck disease using T-2 toxin and selenium deficiency conditions. Rheumatology International 33(1), pp. 157-166. (10.1007/s00296-011-2335-7)
- Li, S., Hayes, A. J., Caterson, B. and Hughes, C. E. 2013. The effect of beta-xylosides on the chondrogenic differentiation of mesenchymal stem cells. Histochemistry and Cell Biology 139(1), pp. 59-74. (10.1007/s00418-012-1017-1)
- Bondeson, J., Wainwright, S. D., Caterson, B. and Hughes, C. E. 2013. ADAMTS5. In: Rawlings, N. D. and Salvesen, G. eds. Handbook of Proteolytic Enzymes. 3rd ed.., Vol. 1. London: Academic Press, pp. 1174-1180., (10.1016/B978-0-12-382219-2.00263-5)
- Bondeson, J., Wainwright, S. D., Caterson, B. and Hughes, C. E. 2013. ADAMTS4. In: Rawlings, N. D. and Salvesen, G. eds. Handbook of Proteolytic Enzymes. 3rd ed.., Vol. 1. London: Academic Press, pp. 1166-1173., (10.1016/B978-0-12-382219-2.00262-3)
2012
- Melrose, J., Isaacs, M. D., Smith, S. M., Hughes, C. E., Little, C. B., Caterson, B. and Hayes, A. J. 2012. Chondroitin sulphate and heparan sulphate sulphation motifs and their proteoglycans are involved in articular cartilage formation during human foetal knee joint development. Histochemistry and Cell Biology 138(3), pp. 461-475. (10.1007/s00418-012-0968-6)
- Wainwright, S. D., Bondeson, J., Hughes, C. E. and Caterson, B. 2012. Human osteoarthritis synovium contains an alternatively spliced transcript of ADAMTS4 [Abstract]. Osteoarthritis and Cartilage 20(S1), pp. S136. (10.1016/j.joca.2012.02.185)
- Serpi, M. et al. 2012. Novel phosphoramidate prodrugs of N-Acetyl-(d)-Glucosamine with antidegenerative activity on bovine and human cartilage explants. Journal of Medicinal Chemistry 55(10), pp. 4629-4639. (10.1021/jm300074y)
- Li, S., Cao, J., Caterson, B. and Hughes, C. E. 2012. Proteoglycan metabolism, cell death and Kashin-Beck Disease. Glycoconjugate Journal 29(5-6), pp. 241-248. (10.1007/s10719-012-9421-2)
2011
- Hayes, A. J., Hughes, C. E., Ralphs, J. R. and Caterson, B. 2011. Chondroitin sulphate sulphation motif expression in the ontogeny of the intervertebral disc. European Cells and Materials 21, pp. 1-14.
- Hayes, A. J., Isaacs, M. D., Hughes, C. E., Caterson, B. and Ralphs, J. R. 2011. Collagen fibrillogenesis in the development of the annulus fibrosus of the intervertebral disc. European Cells and Materials 22, pp. 226-241.
2010
- Bondeson, J., Blom, A. B., Wainwright, S. D., Hughes, C., Caterson, B. and van den Berg, W. B. 2010. The role of synovial macrophages and macrophage-produced mediators in driving inflammatory and destructive responses in osteoarthritis. Arthritis & Rheumatism 62(3), pp. 647-657. (10.1002/art.27290)
- Liles, M. et al. 2010. Differential relative sulfation of keratan sulfate glycosaminoglycan in the chick cornea during embryonic development. Investigative Ophthalmology and Visual Science 51(3), pp. 1365-1372. (10.1167/iovs.09-4004)
- Hurst, S., Zainal, Z., Caterson, B., Hughes, C. E. and Harwood, J. L. 2010. Dietary fatty acids and arthritis. Prostaglandins Leukotrienes & Essential Fatty Acids 82(4-6), pp. 315-318. (10.1016/j.plefa.2010.02.008)
- Zhang, A. et al. 2010. Effects of moniliformin and selenium on human articular cartilage metabolism and their potential relationships to the pathogenesis of Kashin-Beck disease. Journal of Zhejiang University-Science B 11(3), pp. 200-208. (10.1631/jzus.B0900074)
- Ralphs, J. R., Caterson, B., Hughes, C. E. and Hayes, A. J. 2010. Chondroitin sulphate sulfation motifs in intervertebral disc development [Abstract]. European Cells and Materials 20(Supp 2), pp. 3.
2009
- Zainal, Z., Longman, A. J., Hurst, S., Duggan, K., Caterson, B., Hughes, C. E. and Harwood, J. L. 2009. Relative efficacies of omega-3 polyunsaturated fatty acids in reducing expression of key proteins in a model system for studying osteoarthritis. Osteoarthritis and Cartilage 17(7), pp. 896-905. (10.1016/j.joca.2008.12.009)
- Clarkin, C. E. et al. 2009. Phenotypic plasticity of superficial zone chondrocytes is revealed by increased glycosaminoglycan release and a unique angiogenic secretory profile from neo-cartilage grafts [Abstract]. International Journal of Experimental Pathology 90(2), pp. A103-A104. (10.1111/j.1365-2613.2009.00644.x)
- Roberts, H. C. et al. 2009. Chemically modified glucosamine inhibits the release of proteoglycan in a model system of articular cartilage degradation. International Journal of Experimental Pathology 90(1), pp. A78-A79.
- Roberts, H. C. et al. 2009. Chemically modified glucosamine inhibits the release of proteoglycan in a model system of articular cartilage degradation [Abstract]. International Journal of Experimental Pathology 90(1), pp. A78-A79. (10.1111/j.1365-2613.2008.00612.x)
- Zainal, Z., Longman, A. J., Hurst, S., Duggan, K., Hughes, C. E., Caterson, B. and Harwood, J. 2009. Modification of Palm Oil for Anti-Inflammatory Nutraceutical Properties. Lipids 44(7), pp. 581-592. (10.1007/s11745-009-3304-8)
- Rees, S. G. et al. 2009. Immunolocalisation and expression of keratocan in tendon. Osteoarthritis and Cartilage 17(2), pp. 276-279. (10.1016/j.joca.2008.07.007)
2008
- Melrose, J. et al. 2008. Fragmentation of decorin, biglycan, lumican and keratocan is elevated in degenerate human meniscus, knee and hip articular cartilages compared with age-matched macroscopically normal and control tissues. Arthritis Research & Therapy 10(4), article number: R79. (10.1186/ar2453)
- Hayes, A. J., Hughes, C. E. and Caterson, B. 2008. Antibodies and immunohistochemistry in extracellular matrix research. Methods 45(1), pp. 10-21. (10.1016/j.ymeth.2008.01.011)
- McGuigan, C. et al. 2008. Phosphate prodrugs derived from N-acetylglucosamine have enhanced chondroprotective activity in explant cultures and represent a new lead in antiosteoarthritis drug discovery. Journal of Medicinal Chemistry 51(18), pp. 5807-5812. (10.1021/jm800594c)
- Cao, J. et al. 2008. Articular cartilage metabolism in patients with Kashin-Beck Disease: an endemic osteoarthropathy in China. Osteoarthritis and Cartilage 16(6), pp. 680-8. (10.1016/j.joca.2007.09.002)
- Li, S., Cao, J., Shi, Z., Chen, J., Zhang, Z., Hughes, C. E. and Caterson, B. 2008. Promotion of the articular cartilage proteoglycan degradation by T-2 toxin and selenium protective effect. Journal of Zhejiang University-Science B 9(1), pp. 22-33. (10.1631/jzus.B071322)
- Caterson, B., Hayes, A. J., Tudor, D., Nowell, M. A. and Hughes, C. E. 2008. Chondroitin sulphate motifs as biomarkers for the stem/progenitor cell niche in musculoskeletal tissues. European Cells and Materials 16(Supp 2), pp. 47-47.
- Bondeson, J., Wainwright, S. D., Hughes, C. E. and Caterson, B. 2008. The regulation of ADAMTS4 and ADAMTS5 aggrecanases in osteoarthritis: a review. Clinical and Experimental Rheumatology 26(1), pp. 139-145.
- Akhtar, S., Kerr, B., Hayes, A. J., Hughes, C. E., Meek, K. M. and Caterson, B. 2008. Immunochemical localisation of keratan sulphate proteoglycans in cornea, sclera and limbus using a keratanase generated neoepitope monoclonal antibody. Investigative Ophthalmology and Visual Science 49(6), pp. 2424-2431. (10.1167/iovs.06-1498)
- Hayes, A. J., Tudor, D., Nowell, M. A., Caterson, B. and Hughes, C. E. 2008. Chondroitin sulfate sulfation motifs as putative biomarkers for isolation of articular cartilage progenitor cells. Journal of Histochemistry & Cytochemistry 56(2), pp. 125-38. (10.1369/jhc.7A7320.2007)
2007
- Powell, A. J., Little, C. B. and Hughes, C. E. 2007. Low molecular weight isoforms of the aggrecanases are responsible for the cytokine-induced proteolysis of aggrecan in a porcine chondrocyte culture system.. Arthritis & Rheumatism 56(9), pp. 3010-3019. (10.1002/art.22818)
- Bondeson, J. et al. 2007. Adenoviral gene transfer of the endogenous inhibitor IkappaBalpha into human osteoarthritis synovial fibroblasts demonstrates that several matrix metalloproteinases and aggrecanases are nuclear factor-kappaB-dependent. The Journal of Rheumatology 34(3), pp. 523-533.
- Gendron, C. et al. 2007. Proteolytic activities of human ADAMTS-5: Comparative studies wth ADAMTS - 4. Journal of Biological Chemistry 282(25), pp. 18294-18306. (10.1074/jbc.M701523200)
- Gealy, E. C. et al. 2007. Differential expression of the keratan sulphate proteoglycan, keratocan, during chick corneal embryogenesis. Histochemistry and Cell Biology 128(6), pp. 551-555. (10.1007/s00418-007-0332-4)
- Jones, A. R. et al. 2007. Binding and localization of recombinant lubricin to articular cartilage surfaces. Journal of Orthopaedic Research 25(3), pp. 283-292. (10.1002/jor.20325)
- Gendron, C. et al. 2007. Proteolytic activities of human ADAMTS-5. comparative studies with human ADAMTS-4 [Erratum]. World Journal of Biological Chemistry 282(38), pp. 28296.
2006
- Bondeson, J., Wainwright, S. D., Lauder, S. N., Amos, N. and Hughes, C. E. 2006. The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis. Arthritis Research and Therapy 8(6), pp. 187-199. (10.1186/ar2099)
- Hayashida, Y. et al. 2006. Matrix morphogenesis in cornea is mediated by the modification of keratan sulfate by GlcNAc 6-O-sulfotransferase. PNAS 103(36), pp. 13333-13338. (10.1073/pnas.0605441103)
- Wainwright, S. D., Bondeson, J. and Hughes, C. E. 2006. An alternative spliced transcript of ADAMTS4 is present in human synovium from OA patients. Matrix Biology 25(5), pp. 317-320. (10.1016/j.matbio.2006.03.006)
- Grau, S. et al. 2006. The role of human HtrA1 in arthritic disease. The Journal of Biological Chemistry 281(10), pp. 6124-6129. (10.1074/jbc.M500361200)
2005
- Little, C. B., Flannery, C. R., Hughes, C. E., Goodship, A. and Caterson, B. 2005. Cytokine induced metalloproteinase expression and activity does not correlate with focal susceptibility of articular cartilage to degeneration. Osteoarthritis and Cartilage 13(2) (10.1016/j.joca.2004.10.014)
- Hayes, A. J., Tudor, D., Nowell, M. A., Hughes, C. E. and Caterson, B. 2005. Novel chondroitin sulphation motifs as putative biomarkers of articular cartilage chondroprogenitor cells [Abstract]. European Cells and Materials 10(Supp 2), pp. 72.
- Innes, J. F., Little, C. B., Hughes, C. E. and Caterson, B. 2005. Products resulting from cleavage of the interglobular domain of aggrecan in samples of synovial fluid collected from dogs with early- and late-stage osteoarthritis. American Journal of Veterinary Research 66(10), pp. 1679-1685. (10.2460/ajvr.2005.66.1679)
2004
- Kashiwagi, M., Enghild, J. J., Gendron, C., Hughes, C. E., Caterson, B., Itoh, Y. and Nagase, H. 2004. Altered proteolytic activities of ADAMTS-4 expressed by C-terminal processing. Journal of Biological Chemistry 279(11), pp. 10109-10119. (10.1074/jbc.M312123200)
- Kashiwagi, M., Enghild, J. J., Gendron, C., Hughes, C., Caterson, B., Itoh, Y. and Nagase, H. 2004. Altered proteolytic activities of ADAMTS-4 expressed by C-terminal processing [Erratum]. World Journal of Biological Chemistry 279(21), pp. 22786.
2003
- Harris, C. L., Hughes, C. E., Williams, A. S., Goodfellow, I., Evans, D. J., Caterson, B. and Morgan, B. P. 2003. Generation of anti-complement 'prodrugs': cleavable reagents for specific delivery of complement regulators to disease sites. The Journal of Biological Chemistry 278(38), pp. 36068-36076. (10.1074/jbc.M306351200)
- Dart, A. J. et al. 2003. Recombinant equine growth hormone administration: effects on synovial fluid biomarkers and cartilage metabolism in horses. Equine Veterinary Journal 35(3), pp. 302-307. (10.2746/042516403776148165)
- Hughes, C. E., Little, C. B. and Caterson, B. 2003. Measurement of aggrecanase-generated interglobular domain catabolites in the medium and extracts of cartilage explants using Western blot analysis. In: Winyard, P. G. and Willoughby, D. A. eds. Inflammation Protocols., Vol. 225. Methods in Molecular Biology Humana Press, pp. 89-98., (10.1385/1-59259-374-7:89)
- Gendron, C., Kashiwagi, M., Hughes, C. E., Caterson, B. and Nagase, H. 2003. TIMP-3 inhibits aggrecanase-mediated glycosaminoglycan release from cartilage explants stimulated by catabolic factors. FEBS Letters 555(3), pp. 431-436. (10.1016/S0014-5793(03)01295-X)
2002
- Rees, S. G., Davies, J. R., Tudor, D., Flannery, C. R., Hughes, C. E., Dent, C. M. and Caterson, B. 2002. Immunolocalisation and expression of proteoglycan 4 (cartilage superficial zone proteoglycan) in tendon. Matrix biology 21(7), pp. 593-602. (10.1016/S0945-053X(02)00056-2)
- Curtis, C. L. et al. 2002. Pathologic indicators of degradation and inflammation in human osteoarthritic cartilage are abrogated by exposure to n-3 fatty acids [RETRACTED]. Arthritis & Rheumatism 46(6), pp. 1544-1553. (10.1002/art.10305)
- Little, C. B., Hughes, C. E., Jones, S. A., Caterson, B. and Flannery, C. A. 2002. Cyclosporin A inhibition of aggrecanase-mediated proteoglycan catabolism in articular cartilage. Arthritis and Rheumatism - 46(1), pp. 124-129.
- Little, C. B. et al. 2002. Matrix metalloproteinases are involved in C-terminal and interglobular domain processing of cartilage aggrecan in late stage cartilage degradation. Matrix biology 21(3), pp. 271-288. (10.1016/S0945-053X(02)00004-5)
- Quantock, A. J., Siegler, V., Hughes, C. E. and Caterson, B. 2002. Keratan sulphate levels during development of the embryonic avian cornea. Investigative Ophthalmology and Visual Science 43(E-Abst)
- Curtis, C. L. et al. 2002. Effects of n-3 fatty acids on cartilage metabolism [RETRACTED]. Proceedings of the Nutrition Society 61(3), pp. 381-389. (10.1079/PNS2002174)
2001
- Little, C. B., Hughes, C. E., Otterness, I. G. and Caterson, B. 2001. Species specificity of neoepitope antibodies to aggrecanase and MMP-generated sequences in the interglobular domain of aggrecan [Poster Abstract]. International Journal of Experimental Pathology 82(6), pp. A12. (10.1046/j.1365-2613.2001.82_6am.x)
2000
- Caterson, B., Flannery, C. R., Hughes, C. E. and Little, C. B. 2000. Mechanisms involved in cartilage proteoglycan catabolism. Matrix Biology 19(4), pp. 333-344. (10.1016/S0945-053X(00)00078-0)
- Curtis, C. L., Hughes, C. E., Flannery, C. R., Little, C. B., Harwood, J. L. and Caterson, B. 2000. n-3 Fatty Acids Specifically Modulate Catabolic Factors Involved in Articular Cartilage Degradation. Journal of Biological Chemistry 275(2), pp. 721-724. (10.1074/jbc.275.2.721)
- Flannery, C. R., Little, C. B., Hughes, C. E., Curtis, C. L., Caterson, B. and Jones, S. A. 2000. IL-6 and its soluble receptor augment aggrecanase-mediated proteoglycan catabolism in articular cartilage. Matrix biology 19(6), pp. 549-553. (10.1016/S0945-053X(00)00111-6)
- Rees, S. G., Flannery, C. R., Little, C. B., Hughes, C. E., Caterson, B. and Dent, C. M. 2000. Catabolism of aggrecan, decorin and biglycan in tendon. Biochemical Journal 350(1), pp. 181-188. (10.1042/0264-6021:3500181)
Adrannau llyfrau
- Bondeson, J., Wainwright, S. D., Caterson, B. and Hughes, C. E. 2013. ADAMTS5. In: Rawlings, N. D. and Salvesen, G. eds. Handbook of Proteolytic Enzymes. 3rd ed.., Vol. 1. London: Academic Press, pp. 1174-1180., (10.1016/B978-0-12-382219-2.00263-5)
- Bondeson, J., Wainwright, S. D., Caterson, B. and Hughes, C. E. 2013. ADAMTS4. In: Rawlings, N. D. and Salvesen, G. eds. Handbook of Proteolytic Enzymes. 3rd ed.., Vol. 1. London: Academic Press, pp. 1166-1173., (10.1016/B978-0-12-382219-2.00262-3)
- Hughes, C. E., Little, C. B. and Caterson, B. 2003. Measurement of aggrecanase-generated interglobular domain catabolites in the medium and extracts of cartilage explants using Western blot analysis. In: Winyard, P. G. and Willoughby, D. A. eds. Inflammation Protocols., Vol. 225. Methods in Molecular Biology Humana Press, pp. 89-98., (10.1385/1-59259-374-7:89)
Erthyglau
- Dintwa, L., Hughes, C. E. and Blain, E. J. 2023. Importance of mechanical cues in regulating musculoskeletal circadian clock rhythmicity: implications for articular cartilage. Physiological Reports 11(15), article number: e15780. (10.14814/phy2.15780)
- Bains, K. K., Ashworth, S., Koudouna, E., Young, R. D., Hughes, C. E. and Quantock, A. J. 2023. Chondroitin sulphate/dermatan sulphate proteoglycans: potential regulators of corneal stem/progenitor cell phenotype in vitro. International Journal of Molecular Sciences 24(3), article number: 2095. (10.3390/ijms24032095)
- Mutoji, K. N., Sun, M., Elliott, G., Moreno, I. Y., Hughes, C., Gesteira, T. F. and Coulson-Thomas, V. J. 2021. Extracellular matrix deposition and remodeling after corneal alkali burn in mice. International Journal of Molecular Sciences 22(11), article number: 5708. (10.3390/ijms22115708)
- Allaith, S., Tew, S. R., Hughes, C. E., Clegg, P. D., Canty-Laird, E. G. and Comerford, E. J. 2021. Characterisation of key proteoglycans in the cranial cruciate ligaments (CCLs) from two dog breeds with different predispositions to CCL disease and rupture. The Veterinary Journal 272, article number: 105657. (10.1016/j.tvjl.2021.105657)
- Ashworth, S. et al. 2021. Chondroitin sulfate as a potential modulator of the stem cell niche in cornea. Frontiers in Cell and Developmental Biology 8, article number: 567358. (10.3389/fcell.2020.567358)
- Nandadasa, S. et al. 2020. Vascular dimorphism ensured by regulated proteoglycan dynamics favors rapid umbilical artery closure at birth. eLife 9, article number: e60683. (10.7554/eLife.60683)
- Powell, A. et al. 2017. Do model polymer therapeutics sufficiently diffuse through articular cartilage to be a viable therapeutic route?. Journal of Drug Targeting 25(9-10), pp. 919-926. (10.1080/1061186X.2017.1378660)
- Hayes, A. J., Hughes, C. E., Smith, S. M., Caterson, B., Little, C. B. and Melrose, J. 2016. The CS sulphation motifs 4C3, 7D4, 3B3[-]; and perlecan identify stem cell populations and niches, activated progenitor cells and transitional tissue development in the fetal human elbow. Stem Cells and Development 25(11), pp. 836-847. (10.1089/scd.2016.0054)
- Bascoul-Colombo, C., Garaiova, I., Plummer, S. F., Harwood, J. L., Caterson, B. and Hughes, C. E. 2016. Glucosamine hydrochloride but not chondroitin sulfate prevents cartilage degradation and inflammation induced by interleukin-1α in bovine cartilage explants. Cartilage 7(1), pp. 70-81. (10.1177/1947603515603762)
- Esa, A., Archer, C. W., Caterson, B. and Hughes, C. E. 2015. Investigating the role of Wnt antagonist protein Dkk-1 in the pathogenesis of osteoarthritis [Abstract]. International Journal of Experimental Pathology 96(2), pp. A29-A29. (10.1111/iep.12125)
- Chen, J. et al. 2015. Altered proteolytic activity and expression of mmps and aggrecanases and their inhibitors in Kashin-Beck disease. Journal of Orthopaedic Research 33(1), pp. 47-55. (10.1002/jor.22708)
- Luo, M. et al. 2014. Changes in the metabolism of chondroitin sulfate glycosaminoglycans in articular cartilage from patients with Kashin-Beck disease. Osteoarthritis and Cartilage 22(7), pp. 986-995. (10.1016/j.joca.2014.05.012)
- Wainwright, S. D., Bondeson, J., Caterson, B. and Hughes, C. E. 2013. ADAMTS4_v1 is a splice variant of ADAMTS4 that is expressed as a protein in human synovium and cleaves aggrecan at the interglobular domain. Arthritis & Rheumatism 65(11), pp. 2866-2875. (10.1002/art.38102)
- Shu, C. et al. 2013. The ovine newborn and human foetal intervertebral disc contain perlecan and aggrecan variably substituted with native 7D4 CS sulphation motif: spatiotemporal immunolocalisation and co-distribution with Notch-1 in the human foetal disc. Glycoconjugate Journal 30(7), pp. 717-725. (10.1007/s10719-013-9475-9)
- Guan, F. et al. 2013. Histopathology of chondronecrosis development in knee articular cartilage in a rat model of Kashin-Beck disease using T-2 toxin and selenium deficiency conditions. Rheumatology International 33(1), pp. 157-166. (10.1007/s00296-011-2335-7)
- Li, S., Hayes, A. J., Caterson, B. and Hughes, C. E. 2013. The effect of beta-xylosides on the chondrogenic differentiation of mesenchymal stem cells. Histochemistry and Cell Biology 139(1), pp. 59-74. (10.1007/s00418-012-1017-1)
- Melrose, J., Isaacs, M. D., Smith, S. M., Hughes, C. E., Little, C. B., Caterson, B. and Hayes, A. J. 2012. Chondroitin sulphate and heparan sulphate sulphation motifs and their proteoglycans are involved in articular cartilage formation during human foetal knee joint development. Histochemistry and Cell Biology 138(3), pp. 461-475. (10.1007/s00418-012-0968-6)
- Wainwright, S. D., Bondeson, J., Hughes, C. E. and Caterson, B. 2012. Human osteoarthritis synovium contains an alternatively spliced transcript of ADAMTS4 [Abstract]. Osteoarthritis and Cartilage 20(S1), pp. S136. (10.1016/j.joca.2012.02.185)
- Serpi, M. et al. 2012. Novel phosphoramidate prodrugs of N-Acetyl-(d)-Glucosamine with antidegenerative activity on bovine and human cartilage explants. Journal of Medicinal Chemistry 55(10), pp. 4629-4639. (10.1021/jm300074y)
- Li, S., Cao, J., Caterson, B. and Hughes, C. E. 2012. Proteoglycan metabolism, cell death and Kashin-Beck Disease. Glycoconjugate Journal 29(5-6), pp. 241-248. (10.1007/s10719-012-9421-2)
- Hayes, A. J., Hughes, C. E., Ralphs, J. R. and Caterson, B. 2011. Chondroitin sulphate sulphation motif expression in the ontogeny of the intervertebral disc. European Cells and Materials 21, pp. 1-14.
- Hayes, A. J., Isaacs, M. D., Hughes, C. E., Caterson, B. and Ralphs, J. R. 2011. Collagen fibrillogenesis in the development of the annulus fibrosus of the intervertebral disc. European Cells and Materials 22, pp. 226-241.
- Bondeson, J., Blom, A. B., Wainwright, S. D., Hughes, C., Caterson, B. and van den Berg, W. B. 2010. The role of synovial macrophages and macrophage-produced mediators in driving inflammatory and destructive responses in osteoarthritis. Arthritis & Rheumatism 62(3), pp. 647-657. (10.1002/art.27290)
- Liles, M. et al. 2010. Differential relative sulfation of keratan sulfate glycosaminoglycan in the chick cornea during embryonic development. Investigative Ophthalmology and Visual Science 51(3), pp. 1365-1372. (10.1167/iovs.09-4004)
- Hurst, S., Zainal, Z., Caterson, B., Hughes, C. E. and Harwood, J. L. 2010. Dietary fatty acids and arthritis. Prostaglandins Leukotrienes & Essential Fatty Acids 82(4-6), pp. 315-318. (10.1016/j.plefa.2010.02.008)
- Zhang, A. et al. 2010. Effects of moniliformin and selenium on human articular cartilage metabolism and their potential relationships to the pathogenesis of Kashin-Beck disease. Journal of Zhejiang University-Science B 11(3), pp. 200-208. (10.1631/jzus.B0900074)
- Ralphs, J. R., Caterson, B., Hughes, C. E. and Hayes, A. J. 2010. Chondroitin sulphate sulfation motifs in intervertebral disc development [Abstract]. European Cells and Materials 20(Supp 2), pp. 3.
- Zainal, Z., Longman, A. J., Hurst, S., Duggan, K., Caterson, B., Hughes, C. E. and Harwood, J. L. 2009. Relative efficacies of omega-3 polyunsaturated fatty acids in reducing expression of key proteins in a model system for studying osteoarthritis. Osteoarthritis and Cartilage 17(7), pp. 896-905. (10.1016/j.joca.2008.12.009)
- Clarkin, C. E. et al. 2009. Phenotypic plasticity of superficial zone chondrocytes is revealed by increased glycosaminoglycan release and a unique angiogenic secretory profile from neo-cartilage grafts [Abstract]. International Journal of Experimental Pathology 90(2), pp. A103-A104. (10.1111/j.1365-2613.2009.00644.x)
- Roberts, H. C. et al. 2009. Chemically modified glucosamine inhibits the release of proteoglycan in a model system of articular cartilage degradation. International Journal of Experimental Pathology 90(1), pp. A78-A79.
- Roberts, H. C. et al. 2009. Chemically modified glucosamine inhibits the release of proteoglycan in a model system of articular cartilage degradation [Abstract]. International Journal of Experimental Pathology 90(1), pp. A78-A79. (10.1111/j.1365-2613.2008.00612.x)
- Zainal, Z., Longman, A. J., Hurst, S., Duggan, K., Hughes, C. E., Caterson, B. and Harwood, J. 2009. Modification of Palm Oil for Anti-Inflammatory Nutraceutical Properties. Lipids 44(7), pp. 581-592. (10.1007/s11745-009-3304-8)
- Rees, S. G. et al. 2009. Immunolocalisation and expression of keratocan in tendon. Osteoarthritis and Cartilage 17(2), pp. 276-279. (10.1016/j.joca.2008.07.007)
- Melrose, J. et al. 2008. Fragmentation of decorin, biglycan, lumican and keratocan is elevated in degenerate human meniscus, knee and hip articular cartilages compared with age-matched macroscopically normal and control tissues. Arthritis Research & Therapy 10(4), article number: R79. (10.1186/ar2453)
- Hayes, A. J., Hughes, C. E. and Caterson, B. 2008. Antibodies and immunohistochemistry in extracellular matrix research. Methods 45(1), pp. 10-21. (10.1016/j.ymeth.2008.01.011)
- McGuigan, C. et al. 2008. Phosphate prodrugs derived from N-acetylglucosamine have enhanced chondroprotective activity in explant cultures and represent a new lead in antiosteoarthritis drug discovery. Journal of Medicinal Chemistry 51(18), pp. 5807-5812. (10.1021/jm800594c)
- Cao, J. et al. 2008. Articular cartilage metabolism in patients with Kashin-Beck Disease: an endemic osteoarthropathy in China. Osteoarthritis and Cartilage 16(6), pp. 680-8. (10.1016/j.joca.2007.09.002)
- Li, S., Cao, J., Shi, Z., Chen, J., Zhang, Z., Hughes, C. E. and Caterson, B. 2008. Promotion of the articular cartilage proteoglycan degradation by T-2 toxin and selenium protective effect. Journal of Zhejiang University-Science B 9(1), pp. 22-33. (10.1631/jzus.B071322)
- Caterson, B., Hayes, A. J., Tudor, D., Nowell, M. A. and Hughes, C. E. 2008. Chondroitin sulphate motifs as biomarkers for the stem/progenitor cell niche in musculoskeletal tissues. European Cells and Materials 16(Supp 2), pp. 47-47.
- Bondeson, J., Wainwright, S. D., Hughes, C. E. and Caterson, B. 2008. The regulation of ADAMTS4 and ADAMTS5 aggrecanases in osteoarthritis: a review. Clinical and Experimental Rheumatology 26(1), pp. 139-145.
- Akhtar, S., Kerr, B., Hayes, A. J., Hughes, C. E., Meek, K. M. and Caterson, B. 2008. Immunochemical localisation of keratan sulphate proteoglycans in cornea, sclera and limbus using a keratanase generated neoepitope monoclonal antibody. Investigative Ophthalmology and Visual Science 49(6), pp. 2424-2431. (10.1167/iovs.06-1498)
- Hayes, A. J., Tudor, D., Nowell, M. A., Caterson, B. and Hughes, C. E. 2008. Chondroitin sulfate sulfation motifs as putative biomarkers for isolation of articular cartilage progenitor cells. Journal of Histochemistry & Cytochemistry 56(2), pp. 125-38. (10.1369/jhc.7A7320.2007)
- Powell, A. J., Little, C. B. and Hughes, C. E. 2007. Low molecular weight isoforms of the aggrecanases are responsible for the cytokine-induced proteolysis of aggrecan in a porcine chondrocyte culture system.. Arthritis & Rheumatism 56(9), pp. 3010-3019. (10.1002/art.22818)
- Bondeson, J. et al. 2007. Adenoviral gene transfer of the endogenous inhibitor IkappaBalpha into human osteoarthritis synovial fibroblasts demonstrates that several matrix metalloproteinases and aggrecanases are nuclear factor-kappaB-dependent. The Journal of Rheumatology 34(3), pp. 523-533.
- Gendron, C. et al. 2007. Proteolytic activities of human ADAMTS-5: Comparative studies wth ADAMTS - 4. Journal of Biological Chemistry 282(25), pp. 18294-18306. (10.1074/jbc.M701523200)
- Gealy, E. C. et al. 2007. Differential expression of the keratan sulphate proteoglycan, keratocan, during chick corneal embryogenesis. Histochemistry and Cell Biology 128(6), pp. 551-555. (10.1007/s00418-007-0332-4)
- Jones, A. R. et al. 2007. Binding and localization of recombinant lubricin to articular cartilage surfaces. Journal of Orthopaedic Research 25(3), pp. 283-292. (10.1002/jor.20325)
- Gendron, C. et al. 2007. Proteolytic activities of human ADAMTS-5. comparative studies with human ADAMTS-4 [Erratum]. World Journal of Biological Chemistry 282(38), pp. 28296.
- Bondeson, J., Wainwright, S. D., Lauder, S. N., Amos, N. and Hughes, C. E. 2006. The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis. Arthritis Research and Therapy 8(6), pp. 187-199. (10.1186/ar2099)
- Hayashida, Y. et al. 2006. Matrix morphogenesis in cornea is mediated by the modification of keratan sulfate by GlcNAc 6-O-sulfotransferase. PNAS 103(36), pp. 13333-13338. (10.1073/pnas.0605441103)
- Wainwright, S. D., Bondeson, J. and Hughes, C. E. 2006. An alternative spliced transcript of ADAMTS4 is present in human synovium from OA patients. Matrix Biology 25(5), pp. 317-320. (10.1016/j.matbio.2006.03.006)
- Grau, S. et al. 2006. The role of human HtrA1 in arthritic disease. The Journal of Biological Chemistry 281(10), pp. 6124-6129. (10.1074/jbc.M500361200)
- Little, C. B., Flannery, C. R., Hughes, C. E., Goodship, A. and Caterson, B. 2005. Cytokine induced metalloproteinase expression and activity does not correlate with focal susceptibility of articular cartilage to degeneration. Osteoarthritis and Cartilage 13(2) (10.1016/j.joca.2004.10.014)
- Hayes, A. J., Tudor, D., Nowell, M. A., Hughes, C. E. and Caterson, B. 2005. Novel chondroitin sulphation motifs as putative biomarkers of articular cartilage chondroprogenitor cells [Abstract]. European Cells and Materials 10(Supp 2), pp. 72.
- Innes, J. F., Little, C. B., Hughes, C. E. and Caterson, B. 2005. Products resulting from cleavage of the interglobular domain of aggrecan in samples of synovial fluid collected from dogs with early- and late-stage osteoarthritis. American Journal of Veterinary Research 66(10), pp. 1679-1685. (10.2460/ajvr.2005.66.1679)
- Kashiwagi, M., Enghild, J. J., Gendron, C., Hughes, C. E., Caterson, B., Itoh, Y. and Nagase, H. 2004. Altered proteolytic activities of ADAMTS-4 expressed by C-terminal processing. Journal of Biological Chemistry 279(11), pp. 10109-10119. (10.1074/jbc.M312123200)
- Kashiwagi, M., Enghild, J. J., Gendron, C., Hughes, C., Caterson, B., Itoh, Y. and Nagase, H. 2004. Altered proteolytic activities of ADAMTS-4 expressed by C-terminal processing [Erratum]. World Journal of Biological Chemistry 279(21), pp. 22786.
- Harris, C. L., Hughes, C. E., Williams, A. S., Goodfellow, I., Evans, D. J., Caterson, B. and Morgan, B. P. 2003. Generation of anti-complement 'prodrugs': cleavable reagents for specific delivery of complement regulators to disease sites. The Journal of Biological Chemistry 278(38), pp. 36068-36076. (10.1074/jbc.M306351200)
- Dart, A. J. et al. 2003. Recombinant equine growth hormone administration: effects on synovial fluid biomarkers and cartilage metabolism in horses. Equine Veterinary Journal 35(3), pp. 302-307. (10.2746/042516403776148165)
- Gendron, C., Kashiwagi, M., Hughes, C. E., Caterson, B. and Nagase, H. 2003. TIMP-3 inhibits aggrecanase-mediated glycosaminoglycan release from cartilage explants stimulated by catabolic factors. FEBS Letters 555(3), pp. 431-436. (10.1016/S0014-5793(03)01295-X)
- Rees, S. G., Davies, J. R., Tudor, D., Flannery, C. R., Hughes, C. E., Dent, C. M. and Caterson, B. 2002. Immunolocalisation and expression of proteoglycan 4 (cartilage superficial zone proteoglycan) in tendon. Matrix biology 21(7), pp. 593-602. (10.1016/S0945-053X(02)00056-2)
- Curtis, C. L. et al. 2002. Pathologic indicators of degradation and inflammation in human osteoarthritic cartilage are abrogated by exposure to n-3 fatty acids [RETRACTED]. Arthritis & Rheumatism 46(6), pp. 1544-1553. (10.1002/art.10305)
- Little, C. B., Hughes, C. E., Jones, S. A., Caterson, B. and Flannery, C. A. 2002. Cyclosporin A inhibition of aggrecanase-mediated proteoglycan catabolism in articular cartilage. Arthritis and Rheumatism - 46(1), pp. 124-129.
- Little, C. B. et al. 2002. Matrix metalloproteinases are involved in C-terminal and interglobular domain processing of cartilage aggrecan in late stage cartilage degradation. Matrix biology 21(3), pp. 271-288. (10.1016/S0945-053X(02)00004-5)
- Quantock, A. J., Siegler, V., Hughes, C. E. and Caterson, B. 2002. Keratan sulphate levels during development of the embryonic avian cornea. Investigative Ophthalmology and Visual Science 43(E-Abst)
- Curtis, C. L. et al. 2002. Effects of n-3 fatty acids on cartilage metabolism [RETRACTED]. Proceedings of the Nutrition Society 61(3), pp. 381-389. (10.1079/PNS2002174)
- Little, C. B., Hughes, C. E., Otterness, I. G. and Caterson, B. 2001. Species specificity of neoepitope antibodies to aggrecanase and MMP-generated sequences in the interglobular domain of aggrecan [Poster Abstract]. International Journal of Experimental Pathology 82(6), pp. A12. (10.1046/j.1365-2613.2001.82_6am.x)
- Caterson, B., Flannery, C. R., Hughes, C. E. and Little, C. B. 2000. Mechanisms involved in cartilage proteoglycan catabolism. Matrix Biology 19(4), pp. 333-344. (10.1016/S0945-053X(00)00078-0)
- Curtis, C. L., Hughes, C. E., Flannery, C. R., Little, C. B., Harwood, J. L. and Caterson, B. 2000. n-3 Fatty Acids Specifically Modulate Catabolic Factors Involved in Articular Cartilage Degradation. Journal of Biological Chemistry 275(2), pp. 721-724. (10.1074/jbc.275.2.721)
- Flannery, C. R., Little, C. B., Hughes, C. E., Curtis, C. L., Caterson, B. and Jones, S. A. 2000. IL-6 and its soluble receptor augment aggrecanase-mediated proteoglycan catabolism in articular cartilage. Matrix biology 19(6), pp. 549-553. (10.1016/S0945-053X(00)00111-6)
- Rees, S. G., Flannery, C. R., Little, C. B., Hughes, C. E., Caterson, B. and Dent, C. M. 2000. Catabolism of aggrecan, decorin and biglycan in tendon. Biochemical Journal 350(1), pp. 181-188. (10.1042/0264-6021:3500181)
Ymchwil
Cartilage Proteoglycan Metabolism in Osteoarthritis
The synovial joint is a complex structure composed of a number of component specialized connective tissues. Research is directed at understanding the mechanisms underlying the pathological changes that occur in the articular cartilage and synovial joint cavity lining during the progression of osteoarthritis. Research in our laboratories has focused on studying the role that the metalloproteinases belonging to the ADAMTS (a disintegrin and metallo with thrombospondin) family (namely ADAMTS4 and ADAMTS5) have in the cleavage of aggrecan a key process in the pathology of osteoarthritis
Articular cartilage chondrocytes are responsible for the synthesis, organization and maintenance of a specialized extracellular matrix composed predominantly of type II collagen fibrils enmeshing large, multimolecular aggregates of cartilage proteoglycan (aggrecan) bound to hyaluronan (HA) and stabilized by cartilage link protein. The entrapment of the large, highly hydrated proteoglycan aggregates within the collagen fibril meshwork provides articular cartilage with its ability to resist compressive loads applied to the joint during articulation. Maintenance of the components of cartilage extracellular matrix is controlled by the resident chondrocytes that must balance synthetic and degradative processes in order to maintain the integrity of this specialized tissue.
Organisation of Human Aggrecan
The synovial lining of the joint capsule is responsible for maintaining nutrient supply to the articular cartilage and also maintaining low friction during movement through the presence of high concentration of hyaluronan. During the disease process the tissue becomes inflamed and is a contributing factor to the breakdown of articular cartilage.
The research approaches in our laboratories have:
- Focused towards bettering our understanding of the role and mechanisms by which the ADAMTS proteinases are involved in the destruction of aggrecan in cartilage.
- Investigating potential biomarkers that can be used for diagnosis, distinguishing disease progression and monitoring the efficacy of surgical and therapeutic interventions.
We use a multi disciplinary approach in our work that encompasses the use of monoclonal antibody technologies, protein isolation, purification and characterisation and molecular biology techniques. We are using an established panel of neoepitope antibodies to study the catabolic products generated by ADAMTS proteinases in articular cartilage in both in vitro culture systems (which mimic degradative processes during disease) as well as synovial fluids from patients diagnosed with different joint pathologies. This work will ultimately lead to the discovery of specific markers for joint diseases and therefore aid in the development of pharmaceutical inhibitors of key enzymes such as aggrecanase(s) which will then be developed for use in humans, thereby preventing or limiting the progression of cartilage erosion in osteoarthritis.
In addition, we are using monoclonal antibodies recognising the aggrecanases to elucidate the mechanism by which these enzymes are produced and processed during normal tissue homeostasis and in disease. Molecular Biology approaches have led to the discovery of an alternative-splice variant of ADAMTS-4 found only in cells derived from the synovial lining of patients diagnosed with osteoarthritis. Furthermore, the large panel of monoclonal antibodies we have produced are now being used to develop ELISA-based assay kits for identification of biomarkers expressed in the pathogenesis of musculoskeletal diseases.
Current sources of funding
- Arthritis Research UK
- Industry
Collaborations
- Professor John Harwood
- Professor Sally Roberts
- Professor James Richardson
- Professor Hideaki Nagase
Affiliated staff
- Dr Anthony Hayes
- Dr Shane Wainwright
- Dr Laurence Glennon-Alty
Contact Details
+44 29208 76417
Adeilad Syr Martin Evans, Ystafell Cardiff School of Biosciences, The Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, Rhodfa'r Amgueddfa, Caerdydd, CF10 3AX