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New Therapeutic Strategies for Osteoarthritis by Targeting Sialic Acid Receptors

AuthorsCarpintero-Fernandez, Paula; Varela-Eirin, Marta; Lacetera, Alessandra; Gago-Fuentes, Raquel; Fonseca, Eduardo; Martín-Santamaría, Sonsoles ; Mayán-Santos, María Dolores
KeywordsArticular chondrocyte
Molecular modelling
Issue Date2020
PublisherMultidisciplinary Digital Publishing Institute
CitationBiomolecules 10(4): 637 (2020)
AbstractOsteoarthritis (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.
Description© 2020 by the authors.
Publisher version (URL)https://doi.org/10.3390/biom10040637
Appears in Collections:(CIB) Artículos
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