PMID- 32361653 OWN - NLM STAT- MEDLINE DCOM- 20210310 LR - 20210310 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 84 DP - 2020 Jul TI - The protective effect of myricitrin in osteoarthritis: An in vitro and in vivo study. PG - 106511 LID - S1567-5769(19)32369-0 [pii] LID - 10.1016/j.intimp.2020.106511 [doi] AB - Osteoarthritis (OA) is a long-term, chronic, progressive joint condition caused by a pathology characterized by the deterioration of joint cartilage and proliferation of subchondral bone. Myricitrin (Myr) is a flavonoid compound extracted from myrica rubra with potent anti-inflammatory properties, as demonstrated in various studies. However, the mechanisms by which Myr plays a protective role in OA are not completely understood. In this study, the anti-inflammatory properties and potential mechanisms of Myr on mouse chondrocytes treated with interleukin (IL) -1beta (beta) were explored in vitro and the role of Myr in a mouse model of OA in vivo. The production of pro-inflammatory factors, such as IL-6, tumor necrosis factor alpha (TNF-alpha), prostaglandin E2 (PGE2) and nitric oxide (NO) were assessed by enzyme linked immunosorbent assay (ELISA) and the Griess reaction. Protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), Collagen-II, matrix metalloproteinase(MMP)-13, MMP-3, thrombospondin motifs 5(ADAMTS5), inhibitor ofnuclear factor kappa-B (IkappaB), p-IkappaB, p65, p-p65, c-jun-terminal kinase (JNK), p-JNK, extracellular regulated protein kinases (ERK), p-ERK, p38 and p-p38 were quantified using Western blot analysis. In the present study, we found that Myr inhibited IL-1beta-induced production of NO and PGE2, expression of MMP-13, MMP-3 and ADAMTS5 and degradation of collagen-II in mouse chondrocytes. Mechanistically, Myr inhibited the activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-kappaB) treated with IL-1beta in mouse chondrocytes. In vivo, Myr decreased OA Research Society International (OARSI) scores in a surgically-induced mouse model of OA. These data suggest that Myr could be developed as a potential therapyfor OA. CI - Copyright (c) 2020. Published by Elsevier B.V. FAU - Yan, Zijian AU - Yan Z AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthpaedics, Wenzhou 325000, Zhejiang Provinece, China; The Second School of Medicine, WenZhou Medical University, Wenzhou, 325000 Zhejiang Province, China. FAU - Lin, Zeng AU - Lin Z AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthpaedics, Wenzhou 325000, Zhejiang Provinece, China; The Second School of Medicine, WenZhou Medical University, Wenzhou, 325000 Zhejiang Province, China. FAU - Wu, Yifan AU - Wu Y AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthpaedics, Wenzhou 325000, Zhejiang Provinece, China; The Second School of Medicine, WenZhou Medical University, Wenzhou, 325000 Zhejiang Province, China. FAU - Zhan, Jingdi AU - Zhan J AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthpaedics, Wenzhou 325000, Zhejiang Provinece, China; The Second School of Medicine, WenZhou Medical University, Wenzhou, 325000 Zhejiang Province, China. FAU - Qi, Weihui AU - Qi W AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthpaedics, Wenzhou 325000, Zhejiang Provinece, China; The Second School of Medicine, WenZhou Medical University, Wenzhou, 325000 Zhejiang Province, China. FAU - Lin, Jian AU - Lin J AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China; The Second School of Medicine, WenZhou Medical University, Wenzhou, 325000 Zhejiang Province, China. FAU - Shen, Jiquan AU - Shen J AD - The Second School of Medicine, WenZhou Medical University, Wenzhou, 325000 Zhejiang Province, China; Department of Orthopaedics, Lishui Municipal People Hospital, Lishui 323000, Zhejiang Province, China. FAU - Xue, Xinghe AU - Xue X AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China. Electronic address: qq524689473@163.com. FAU - Pan, Xiaoyun AU - Pan X AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China. Electronic address: panxy9046@163.com. LA - eng PT - Journal Article DEP - 20200501 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Flavonoids) RN - 0 (NF-kappa B) RN - 5Z0ZO61WPJ (myricitrin) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, mouse) RN - EC 1.14.99.- (Ptgs2 protein, mouse) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.4.24.- (ADAMTS5 Protein) RN - EC 3.4.24.- (Matrix Metalloproteinase 13) RN - EC 3.4.24.- (Mmp13 protein, mouse) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.4.24.17 (Mmp3 protein, mouse) SB - IM MH - ADAMTS5 Protein/metabolism MH - Animals MH - Anti-Inflammatory Agents/pharmacology/*therapeutic use MH - Cells, Cultured MH - Chondrocytes/drug effects/metabolism MH - Cyclooxygenase 2/metabolism MH - Extracellular Matrix/drug effects MH - Flavonoids/pharmacology/*therapeutic use MH - Knee Joint/drug effects/pathology MH - Male MH - Matrix Metalloproteinase 13/metabolism MH - Matrix Metalloproteinase 3/metabolism MH - Mice, Inbred C57BL MH - Mitogen-Activated Protein Kinases/metabolism MH - NF-kappa B/metabolism MH - Nitric Oxide Synthase Type II/metabolism MH - Osteoarthritis/*drug therapy/metabolism/pathology OTO - NOTNLM OT - IL-1beta OT - Inflammation OT - MAPK OT - Myricitrin OT - NF-kappaB COIS- Declaration of Competing Interest The authors declare that they have no conflicts of interest. EDAT- 2020/05/04 06:00 MHDA- 2021/03/11 06:00 CRDT- 2020/05/04 06:00 PHST- 2019/10/19 00:00 [received] PHST- 2020/04/11 00:00 [revised] PHST- 2020/04/12 00:00 [accepted] PHST- 2020/05/04 06:00 [pubmed] PHST- 2021/03/11 06:00 [medline] PHST- 2020/05/04 06:00 [entrez] AID - S1567-5769(19)32369-0 [pii] AID - 10.1016/j.intimp.2020.106511 [doi] PST - ppublish SO - Int Immunopharmacol. 2020 Jul;84:106511. doi: 10.1016/j.intimp.2020.106511. Epub 2020 May 1.