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Open AccessArticle

New Therapeutic Strategies for Osteoarthritis by Targeting Sialic Acid Receptors

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CellCOM Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), CH-Universitario A Coruña (XXIAC), Universidade da Coruña (UDC), Servizo Galego de Saúde (SERGAS), Xubias de Arriba, 84, 15006 A Coruña, Spain
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Department of Structural and Chemical Biology, Centro de Investigaciones Biológicas Margarita Salas CIB-CSIC, C/Ramiro de Maeztu, 9, 28040 Madrid, Spain
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Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(4), 637; https://doi.org/10.3390/biom10040637
Received: 20 March 2020 / Revised: 12 April 2020 / Accepted: 14 April 2020 / Published: 21 April 2020
(This article belongs to the Section Chemical Biology)
Osteoarthritis (OA) is the most common degenerative joint disease characterized by articular cartilage degradation and joint degeneration. 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 α-2,6-linked sialic acids to those that contain α-2,3 was associated with the onset of common types of arthritis. However, the pathophysiology of α-2,3-sialylation in cartilage has not been yet elucidated. We show that cartilage from osteoarthritic patients expresses high levels of the α-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 α-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. View Full-Text
Keywords: articular chondrocyte; cartilage; sialylation; osteoarthritis; arthritis; MASL; podoplanin; glycoproteins; molecular modelling articular chondrocyte; cartilage; sialylation; osteoarthritis; arthritis; MASL; podoplanin; glycoproteins; molecular modelling
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Carpintero-Fernandez, P.; Varela-Eirin, M.; Lacetera, A.; Gago-Fuentes, R.; Fonseca, E.; Martin-Santamaria, S.; Mayan, M.D. New Therapeutic Strategies for Osteoarthritis by Targeting Sialic Acid Receptors. Biomolecules 2020, 10, 637.

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