FRI0429 UROLITHIN B ATTENUATES THE INFLAMMATORY AND NITROSATIVE STRESS ON INTERLEUKIN-1 INDUCED CHONDROCYTES

Background:Osteoarthritis (OA) is one of the most common degenerative disorders with cartilage degradation especially to the elderly resulting in disability. Many inflammatory cytokines involve the pathogenesis of the OA and causes destruction and decomposition of articular cartilage, including interleukin 1 beta (IL-1β). Urolithin B is a small polyphenolic compound, produced by gut flora from ellagitannins-rich foods, such as pomegranate, strawberries, raspberries, etc. Urolithin B has been documented in anti-inflammatory and antioxidant properties. However, the mechanism underlying the effects of Urolithin B on IL-1 stimulated human osteoarthritis (OA) chondrocytes remains unrevealedObjectives:The aim of this study was to investigate the biologic effects of Urolithin B on OA models and associated mechanism.Methods:Primary culture of human chondrocyte, knee joint obtained from total knee replacement of patients with osteoarthritis, were used IL-1β induced and treated with/without 100μM Urolithin B for 24 hours respectively. Total cell lysates were collected for western blotting to analyze the catabolic molecules. Culture medium were collected for gelatin zymography to analyze the secretion of MMP 2 and 9.Results:Urolithin B inhibits the overexpression of not only inflammatory marker COX2 and nitrosative marker NOS2, but also matrix metalloproteinases (MMPs)-1, -3, 13 in IL-1β induced chondrocytes by western blotting. It also restored the IL-1β induced glycosaminoglycan degeneration in ex vivo articular cartilage evaluated by Safranin O stain. Meanwhile, Urolithin B can activate autophagy, increasing LC3 II/I ratio, in IL-1β induced chondrocytes.Conclusion:Collectively, the study demonstrates that Urolithin B may be of value in the treatment of osteoarthritis through its anti-inflammatory, anti-oxidant and anti-proteinase activities.References:[1]Decker, R.S., E. Koyama, and M. Pacifici,Articular Cartilage: Structural and Developmental Intricacies and Questions.Curr Osteoporos Rep, 2015.13(6): p. 407-14.[2]Luo, Y., et al.,The minor collagens in articular cartilage.Protein Cell, 2017.8(8): p. 560-572.[3]Sophia Fox, A.J., A. Bedi, and S.A. Rodeo,The basic science of articular cartilage: structure, composition, and function.Sports Health, 2009.1(6): p. 461-8.[4]Carballo, C.B., et al.,Basic Science of Articular Cartilage.Clin Sports Med, 2017.36(3): p. 413-425.[5]Taruc-Uy, R.L. and S.A. Lynch,Diagnosis and treatment of osteoarthritis.Prim Care, 2013.40(4): p. 821-36, vii.[6]Rhon, D., Re: Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage 2008;16:137-62. Osteoarthritis Cartilage, 2008.16(12): p. 1585; author reply 1589.[7]Wang, S.T., et al., Antimelanogenic Effect of Urolithin A and Urolithin B, the Colonic Metabolites of Ellagic Acid, in B16 Melanoma Cells. J Agric Food Chem, 2017.65(32): p. 6870-6876.Feng-Cheng Wu1, Feng-Cheng Liu2, Chih-Chien Wang3, Yi-Jen Peng1,4*1Graduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei, Taiwan, R.O.C.2Rheumatology, Immunology and Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.3Department of Orthopedic, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.4Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.Title:Urolithin B attenuates the inflammatory and nitrosative stress on interleukin-1 induced chondrocytesKey words:Urolithin B, Osteoarthritis, chondrocytes, Cyclooxygenase 2, Nitric Oxide Synthase 2, matrix metalloproteinaseDisclosure of Interests:None declared