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The articular cartilage is mainly formed by chondrocytes and a collagen-proteoglycan extracellular matrix that contains high levels of glycosylated proteins. It was reported that the shift from glycoproteins containing \u03b1-2,6-linked sialic acids to those that contain \u03b1-2,3 was associated with the onset of common types of arthritis. However, the pathophysiology of \u03b1-2,3-sialylation in cartilage has not been yet elucidated. We show that cartilage from osteoarthritic patients expresses high levels of the \u03b1-2,3-sialylated transmembrane mucin receptor, known as podoplanin (PDPN). Additionally, the Maackia amurensis seed lectin (MASL), that can be utilized to target PDPN, attenuates the inflammatory response mediated by NF-kB activation in primary chondrocytes and protects human cartilage breakdown ex vivo and in an animal model of arthritis. These findings reveal that specific lectins targeting \u03b1-2,3-sialylated receptors on chondrocytes might effectively inhibit cartilage breakdown. We also present a computational 3D molecular model for this interaction. These findings provide mechanistic information on how a specific lectin could be used as a novel therapy to treat degenerative joint diseases such as osteoarthritis.<\/jats:p>","DOI":"10.3390\/biom10040637","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T05:48:52Z","timestamp":1587448132000},"page":"637","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["New Therapeutic Strategies for Osteoarthritis by Targeting Sialic Acid Receptors"],"prefix":"10.3390","volume":"10","author":[{"given":"Paula","family":"Carpintero-Fernandez","sequence":"first","affiliation":[{"name":"CellCOM Research Group, Instituto de Investigaci\u00f3n Biom\u00e9dica de A Coru\u00f1a (INIBIC), CH-Universitario A Coru\u00f1a (XXIAC), Universidade da Coru\u00f1a (UDC), Servizo Galego de Sa\u00fade (SERGAS), Xubias de Arriba, 84, 15006 A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Varela-Eirin","sequence":"additional","affiliation":[{"name":"CellCOM Research Group, Instituto de Investigaci\u00f3n Biom\u00e9dica de A Coru\u00f1a (INIBIC), CH-Universitario A Coru\u00f1a (XXIAC), Universidade da Coru\u00f1a (UDC), Servizo Galego de Sa\u00fade (SERGAS), Xubias de Arriba, 84, 15006 A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Lacetera","sequence":"additional","affiliation":[{"name":"Department of Structural and Chemical Biology, Centro de Investigaciones Biol\u00f3gicas Margarita Salas CIB-CSIC, C\/Ramiro de Maeztu, 9, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Gago-Fuentes","sequence":"additional","affiliation":[{"name":"CellCOM Research Group, Instituto de Investigaci\u00f3n Biom\u00e9dica de A Coru\u00f1a (INIBIC), CH-Universitario A Coru\u00f1a (XXIAC), Universidade da Coru\u00f1a (UDC), Servizo Galego de Sa\u00fade (SERGAS), Xubias de Arriba, 84, 15006 A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8048-2681","authenticated-orcid":false,"given":"Eduardo","family":"Fonseca","sequence":"additional","affiliation":[{"name":"CellCOM Research Group, Instituto de Investigaci\u00f3n Biom\u00e9dica de A Coru\u00f1a (INIBIC), CH-Universitario A Coru\u00f1a (XXIAC), Universidade da Coru\u00f1a (UDC), Servizo Galego de Sa\u00fade (SERGAS), Xubias de Arriba, 84, 15006 A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7679-0155","authenticated-orcid":false,"given":"Sonsoles","family":"Martin-Santamaria","sequence":"additional","affiliation":[{"name":"Department of Structural and Chemical Biology, Centro de Investigaciones Biol\u00f3gicas Margarita Salas CIB-CSIC, C\/Ramiro de Maeztu, 9, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria D.","family":"Mayan","sequence":"additional","affiliation":[{"name":"CellCOM Research Group, Instituto de Investigaci\u00f3n Biom\u00e9dica de A Coru\u00f1a (INIBIC), CH-Universitario A Coru\u00f1a (XXIAC), Universidade da Coru\u00f1a (UDC), Servizo Galego de Sa\u00fade (SERGAS), Xubias de Arriba, 84, 15006 A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1002\/art.34453","article-title":"Osteoarthritis: A disease of the joint as an organ","volume":"64","author":"Loeser","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/nrm3383","article-title":"Vertebrate protein glycosylation: Diversity, synthesis and function","volume":"13","author":"Moremen","year":"2012","journal-title":"Nat. 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