2024-03-28T08:06:27Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/2094372021-12-28T15:49:38Zcom_10261_86com_10261_1col_10261_339
DIGITAL.CSIC
author
Carpintero-Fernandez, Paula
author
Varela-Eirin, Marta
author
Lacetera, Alessandra
author
Gago-Fuentes, Raquel
author
Fonseca, Eduardo
author
Martín-Santamaría, Sonsoles
author
Mayán-Santos, María Dolores
funder
Sociedad Española de Reumatología
funder
Instituto de Salud Carlos III
funder
European Commission
funder
Xunta de Galicia
funder
Asociación Cultural Nogará
funder
Ministerio de Economía y Competitividad (España)
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Agencia Estatal de Investigación (España)
2020-04-28T14:05:35Z
2020-04-28T14:05:35Z
2020
Biomolecules 10(4): 637 (2020)
http://hdl.handle.net/10261/209437
10.3390/biom10040637
2218-273X
http://dx.doi.org/10.13039/501100011033http://dx.doi.org/10.13039/501100000780http://dx.doi.org/10.13039/501100004587http://dx.doi.org/10.13039/501100003329http://dx.doi.org/10.13039/501100010801
32326143
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.
eng
openAccess
Articular chondrocyte
Cartilage
Sialylation
Osteoarthritis
Arthritis
MASL
Podoplanin
Glycoproteins
Molecular modelling
New Therapeutic Strategies for Osteoarthritis by Targeting Sialic Acid Receptors
artículo
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
URL
https://digital.csic.es/bitstream/10261/209437/1/Therapeutic_Carpintero_Art2020.pdf
File
MD5
17bd826b161de6697b0b466ec20305f7
5768635
application/pdf
Therapeutic_Carpintero_Art2020.pdf