New Therapeutic Strategies for Osteoarthritis by Targeting Sialic Acid Receptors
Identificadores
Identificadores
URI: http://hdl.handle.net/20.500.11940/16172
PMID: 32326143
DOI: 10.3390/biom10040637
ISSN: 2218-273X
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Fecha de publicación
2020Título de revista
BIOMOLECULES
Tipo de contenido
Journal Article
DeCS
isoformas de proteínas | unión proteica | animales | glicoproteínas de membranas | lectinas | ácido N-acetilneuramínico | glicoproteínas | transducción de señales | condrocitos | cartílago | matriz extracelular | humanos | células | NF-kappa B | osteoartritis | ratonesMeSH
N-Acetylneuraminic Acid | Lectins | Mice | Chondrocytes | Extracellular Matrix | Signal Transduction | Animals | NF-kappa B | Protein Binding | Osteoarthritis | Protein Isoforms | Glycoproteins | Humans | Cells | Membrane Glycoproteins | CartilageResumen
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 alpha-2,6-linked sialic acids to those that contain alpha-2,3 was associated with the onset of common types of arthritis. However, the pathophysiology of alpha-2,3-sialylation in cartilage has not been yet elucidated. We show that cartilage from osteoarthritic patients expresses high levels of the alpha-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 alpha-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.