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Quercetin prevents osteoarthritis progression possibly via regulation of local and systemic inflammatory cascades
Authors:Haiyan Wang  Yongyong Yan  Janak L. Pathak  Wei Hong  Jing Zeng  Dongyang Qian  Binwei Hao  Haiqing Li  Jinlan Gu  Richard T. Jaspers  Gang Wu  Ming Shao  Gongyong Peng  Haifeng Lan
Affiliation:1. Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China;2. Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China

Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands

Contribution: Data curation (equal), ​Investigation (equal), Writing - original draft (equal);3. Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China

Contribution: Methodology (equal), Writing - review & editing (lead);4. State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China

Contribution: Formal analysis (equal), Funding acquisition (equal);5. Liwan Central Hospital of Guangzhou, Guangzhou, China

Contribution: Resources (equal);6. Department of Orthopaedics, The First Affiliated Hospital, Guangzhou Medical University/Guangdong Key Laboratory of Orthopaedic Technology and Implant Materials, Guangzhou, China

Contribution: Funding acquisition (equal);7. State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

Department of Pulmonary and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, China

Contribution: Formal analysis (equal);8. State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

Contribution: Formal analysis (equal);9. GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China

Contribution: ​Investigation (equal);10. Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China

Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands

Contribution: Writing - review & editing (supporting);11. Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Science, Amsterdam, The Netherlands;12. Department of Orthopaedic Surgery, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China;13. State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

Abstract:Due to the lack of effective treatments, osteoarthritis (OA) remains a challenge for clinicians. Quercetin, a bioflavonoid, has shown potent anti-inflammatory effects. However, its effect on preventing OA progression and the underlying mechanisms are still unclear. In this study, Sprague–Dawley male rats were divided into five groups: control group, OA group (monosodium iodoacetate intra-articular injection), and three quercetin-treated groups. Quercetin-treated groups were treated with intragastric quercetin once a day for 28 days. Gross observation and histopathological analysis showed cartilage degradation and matrix loss in the OA group. High-dose quercetin-group joints showed failure in OA progression. High-dose quercetin inhibited the OA-induced expression of MMP-3, MMP-13, ADAMTS4, and ADAMTS5 and promoted the OA-reduced expression of aggrecan and collagen II. Levels of most inflammatory cytokines and growth factors tested in synovial fluid and serum were upregulated in the OA group and these increases were reversed by high-dose quercetin. Similarly, subchondral trabecular bone was degraded in the OA group and this effect was reversed in the high-dose quercetin group. Our findings indicate that quercetin has a protective effect against OA development and progression possibly via maintaining the inflammatory cascade homeostasis. Therefore, quercetin could be a potential therapeutic agent to prevent OA progression in risk groups.
Keywords:inflammation  osteoarthritis  osteochondral degeneration  pro-inflammatory markers  quercetin
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