AB0100 PREVENTIVE ANTI-INFLAMMATORY EFFECT OF POLYDATIN IN PYROPHOSPHATE CALCIUM CRYSTAL-INDUCED ARTHRITIS IN MICE
Authors: F. Oliviero, P. Galozzi, C. Baggio, V. Lazzarin, G. Ravagnan, P. Sfriso, R. Ramonda, G. Pennelli, A. Doria, R. Luisetto
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The health benefits of plant polyphenols have stimulated a growing interest in the scientific community. Their ability to influence various pathological processes has been demonstrated in several in vitro and in vivo disease models [1]. We have recently shown that polydatin, a stilbenoid and precursor of resveratrol, is capable of preventing calcium pyrophosphate (CPP) crystal-induced arthritis in mice [2]. <h3>Objectives:</h3> The aim of this study was to investigate some potential mechanisms of action associated with this anti-inflammatory effect. <h3>Methods:</h3> Acute arthritis was induced by injection of a suspension of sterile CPP crystals into the ankle joint of Balb/c mice. Animals were randomised to receive polydatin or colchicine (the control drug) according to a prophylactic protocol. Ankle swelling (primary outcome) was measured at different time points before and after CPP injection. Both joints and muscles were harvested at sacrifice. Histological parameters were assessed by H&amp;E, safranin and Masson's trichrome staining. Muscle damage was evaluated by H&amp;E staining, while Kondziela's inverted test was used to assess muscle strength. A cytokine antibody array (Ray-Biotech) was performed on the joint tissue. <h3>Results:</h3> Injection of CPP crystals into the ankle resulted in oedema with evident swelling (primary outcome), moderate areas of leukocyte infiltration, loss of homogeneity of synovial membrane structure, moderate to severe loss of proteoglycan in the superficial hyaline layer of cartilage with damage extending into the underlying region. Mice pretreated with polydatin showed reduced ankle swelling 48 hours after crystal injection, similar to that seen after colchicine pretreatment. This was associated with very limited inflammatory damage, with moderate and focal zones of proteoglycan loss and significant preservation of cartilage and bone structures. Intact cartilage and bone surfaces were observed in untreated joints. Regarding the effect on gastrocnemius muscle, CPP crystals induced leukocyte infiltration, loss of muscle fibres and eosinophilic degenerative fibres with enlarged interstitial areas due to increased muscle oedema. In PD- and colchicine-treated mice, muscle damage was limited and the musculoskeletal structure was generally preserved. The cytokine array showed the activation of different inflammatory pathways after CPP injection. PD showed to strongly influence leukocyte migration (MIP-1G, L-selectin, CXCL16, BLC), angiogenesis (VEGF, VEGF-R2, VEGF-R3, MMP-3) and resolution of inflammation (sTNF-RI, sTNF-RII). <h3>Conclusion:</h3> PD effectively prevents the acute inflammatory response to CPP crystals in mice, preserving both articular and muscular structures. The most affected pathways involve leukocyte migration and the angiogenic process. <h3>REFERENCES:</h3> [1] Oliviero F, Scanu A, Zamudio-Cuevas Y, Punzi L, Spinella P. Anti-inflammatory effects of polyphenols in arthritis. J Sci Food Agric. 2018;98:1653-1659. doi: 10.1002/jsfa.8664. [2] Oliviero F, Galozzi P, Scanu A, et al. Polydatin Prevents Calcium Pyrophosphate Crystal-Induced Arthritis in Mice. Nutrients. 2021;13:929. doi: 10.3390/nu13030929. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>