TY - JOUR T1 - FRI0031 Targeting Sialic Acid-Modified Receptors as A Potential Therapy for Osteoarthritis JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 437 LP - 437 DO - 10.1136/annrheumdis-2016-eular.1688 VL - 75 IS - Suppl 2 AU - P. Carpintero Fernández AU - R. Gago-Fuentes AU - A. Lacetera AU - M. Varela-Eirin AU - B. Acea AU - E. Fonseca AU - S. Martin-Santamaria AU - M.D. Mayán Y1 - 2016/06/01 UR - http://ard.bmj.com/content/75/Suppl_2/437.1.abstract N2 - Background Osteoarthritis (OA) is one of the most common diseases worldwide. Its prevalence and severity increase with age, but treatments only provide symptomatic relief. The articular cartilage consists of a collagen-proteoglycan matrix containing highly glycosylated proteins synthesized by chondrocytes. A notable shift from glycoproteins containing a-2,6-linked sialic acids to those containing a-2,3-linked sialic acids has been associated with progressive cartilage degeneration and with the onset of disorders such as rheumatoid arthritis (RA) and OA1–3. However, the pathophysiology of a-2,3-sialylation in cartilage has not yet been elucidated.Objectives Lectins recognize specific terminal aspects of glycan chains and the Maackia amurensis seed lectin (MASL) is a plant lectin that can bind to sialylated glycoproteins. Here, we study the effects of the lectin MASL on chondrocytes and cartilage integrity from healthy donors, OA patients and animal models of arthritis.Methods Cell viability, cell adhesion and growth were performed using commercial kits. Reactive oxygen species (ROS) levels were measured by DCFH-DA and by Flow Cytometry. Gene expression was analyzed by quantitative real-time PCR. Staining methods were used to study cartilage integrity. Oligomycin and LPS were used to induce cartilage degeneration in vitro and in vivo (human cartilage and mouse model, Mus musculus BALC/c).Results he expression of the a-2,3-sialylated transmembrane mucin receptor podoplanin (PDPN) is induced in cartilage from osteoarthritic patients. Co-immunofluorescence technique showed that MASL can be used to target PDPN. Nanomolar concentrations of MASL protected primary chondrocytes and prevented cartilage breakdown in human tissue from OA patients ex vivo and in an animal model of OA initiated by ROS, inflammatory cytokines, and metalloproteinases. Besides, the increased levels of the α-2,3 sialyltransferase isoforms and the corresponding increase in the levels of a-2,3-sialylated glycoproteins in osteoarthritic chondrocytes may shed mechanistic light on the pathophysiology of OA. These findings based on various experimental models of arthritis reveal that specific lectins that target a-2,3-sialylated transmembrane receptors, such as PDPN on chondrocytes, may effectively inhibit cartilage destruction in the face of various arthritic insults. We also provide a three-dimensional molecular model for such an interaction.Conclusions The ability of MASL to target a-2,3-sialylated glycoproteins, such as PDPN, and to protect chondrocytes from insults leading to cartilage degradation might offer further possibilities for therapeutic interventions and novel arthritis treatments that may include the regulation of sialylation during acute disease stages.Toegel, S. et al. Arthritis Res Ther 15, R147. (2013).Toegel, S. et al. Osteoarthritis Cartilage 18, 240–248. (2010).Toegel, S. et al. In Vitro Cell Dev Biol Anim 45, 351–360. (2009).Disclosure of Interest None declared ER -