Exploration of metformin as novel therapy for osteoarthritis: preventing cartilage degeneration and reducing pain behavior

Abstract Background Metformin could activate adenosine monophosphate-activated protein kinase (AMPK) which was postulated as a potential therapeutic target for osteoarthritis. This study aimed to examine the effects of metformin on cartilage and pain in osteoarthritis mouse model. Methods Eighty 10-...

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Main Authors: Hui Li, Xiang Ding, Robert Terkeltaub, Hang Lin, Yuqing Zhang, Bin Zhou, Ke He, Kun Li, Zhichen Liu, Jie Wei, Yuanheng Yang, Hui Xie, Chao Zeng, Guanghua Lei
Format: Article
Language:English
Published: BMC 2020-02-01
Series:Arthritis Research & Therapy
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13075-020-2129-y
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spelling doaj-a2c4f01b920e44fba99870a88a5df8862020-11-25T02:27:29ZengBMCArthritis Research & Therapy1478-63622020-02-0122111110.1186/s13075-020-2129-yExploration of metformin as novel therapy for osteoarthritis: preventing cartilage degeneration and reducing pain behaviorHui Li0Xiang Ding1Robert Terkeltaub2Hang Lin3Yuqing Zhang4Bin Zhou5Ke He6Kun Li7Zhichen Liu8Jie Wei9Yuanheng Yang10Hui Xie11Chao Zeng12Guanghua Lei13Department of Orthopaedics, Xiangya Hospital, Central South UniversityDepartment of Orthopaedics, Xiangya Hospital, Central South UniversityDepartment of Medicine, University of California at San DiegoCenter for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of MedicineDivision of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical SchoolHunan Key Laboratory of Joint Degeneration and InjuryHunan Key Laboratory of Joint Degeneration and InjuryDepartment of Orthopaedics, Xiangya Hospital, Central South UniversityDepartment of Orthopaedics, Xiangya Hospital, Central South UniversityDivision of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South UniversityDepartment of Orthopaedics, Xiangya Hospital, Central South UniversityDepartment of Orthopaedics, Xiangya Hospital, Central South UniversityDepartment of Orthopaedics, Xiangya Hospital, Central South UniversityAbstract Background Metformin could activate adenosine monophosphate-activated protein kinase (AMPK) which was postulated as a potential therapeutic target for osteoarthritis. This study aimed to examine the effects of metformin on cartilage and pain in osteoarthritis mouse model. Methods Eighty 10-week-old male C57BL/6 mice were randomized to 6 groups: non-operation, sham-operation, destabilization of the medial meniscus (DMM)-operation with intragastric saline/metformin, and DMM-operation with intraarticular saline/metformin. Articular cartilage degeneration was examined by scanning electron microscopy (SEM) and graded using the scoring system recommended by Osteoarthritis Research Society International (OARSI). Mechanical withdrawal threshold and hind paw weight distribution were measured to assess the pain-related behavior. Cell Counting Kit-8 assay, quantificational real-time polymerase chain reaction, and western blot analysis were conducted to examine the anabolic and anti-catabolic effect of metformin and the role of AMPK in mediating its effects on interleukin-1β stimulated primary mice chondrocytes. Results Compared with mice receiving intragastric and intraarticular saline, mice in both intragastric and intraarticular metformin displayed attenuated articular cartilage degeneration, indicated by less cartilage damage under SEM and significantly lower OARSI scores. A higher paw withdrawal threshold and a decreased weight-bearing asymmetry were observed in the intragastric and intraarticular metformin mice compared with their corresponding saline groups in DMM model of osteoarthritis. In vitro experiments showed that metformin not only decreased the level of matrix metalloproteinase 13, but also elevated type II collagen production through activating AMPK pathway. Conclusions Metformin attenuates osteoarthritis structural worsening and modulates pain, suggesting its potential for osteoarthritis prevention or treatment.http://link.springer.com/article/10.1186/s13075-020-2129-yOsteoarthritisMetforminMiceAMPK
collection DOAJ
language English
format Article
sources DOAJ
author Hui Li
Xiang Ding
Robert Terkeltaub
Hang Lin
Yuqing Zhang
Bin Zhou
Ke He
Kun Li
Zhichen Liu
Jie Wei
Yuanheng Yang
Hui Xie
Chao Zeng
Guanghua Lei
spellingShingle Hui Li
Xiang Ding
Robert Terkeltaub
Hang Lin
Yuqing Zhang
Bin Zhou
Ke He
Kun Li
Zhichen Liu
Jie Wei
Yuanheng Yang
Hui Xie
Chao Zeng
Guanghua Lei
Exploration of metformin as novel therapy for osteoarthritis: preventing cartilage degeneration and reducing pain behavior
Arthritis Research & Therapy
Osteoarthritis
Metformin
Mice
AMPK
author_facet Hui Li
Xiang Ding
Robert Terkeltaub
Hang Lin
Yuqing Zhang
Bin Zhou
Ke He
Kun Li
Zhichen Liu
Jie Wei
Yuanheng Yang
Hui Xie
Chao Zeng
Guanghua Lei
author_sort Hui Li
title Exploration of metformin as novel therapy for osteoarthritis: preventing cartilage degeneration and reducing pain behavior
title_short Exploration of metformin as novel therapy for osteoarthritis: preventing cartilage degeneration and reducing pain behavior
title_full Exploration of metformin as novel therapy for osteoarthritis: preventing cartilage degeneration and reducing pain behavior
title_fullStr Exploration of metformin as novel therapy for osteoarthritis: preventing cartilage degeneration and reducing pain behavior
title_full_unstemmed Exploration of metformin as novel therapy for osteoarthritis: preventing cartilage degeneration and reducing pain behavior
title_sort exploration of metformin as novel therapy for osteoarthritis: preventing cartilage degeneration and reducing pain behavior
publisher BMC
series Arthritis Research & Therapy
issn 1478-6362
publishDate 2020-02-01
description Abstract Background Metformin could activate adenosine monophosphate-activated protein kinase (AMPK) which was postulated as a potential therapeutic target for osteoarthritis. This study aimed to examine the effects of metformin on cartilage and pain in osteoarthritis mouse model. Methods Eighty 10-week-old male C57BL/6 mice were randomized to 6 groups: non-operation, sham-operation, destabilization of the medial meniscus (DMM)-operation with intragastric saline/metformin, and DMM-operation with intraarticular saline/metformin. Articular cartilage degeneration was examined by scanning electron microscopy (SEM) and graded using the scoring system recommended by Osteoarthritis Research Society International (OARSI). Mechanical withdrawal threshold and hind paw weight distribution were measured to assess the pain-related behavior. Cell Counting Kit-8 assay, quantificational real-time polymerase chain reaction, and western blot analysis were conducted to examine the anabolic and anti-catabolic effect of metformin and the role of AMPK in mediating its effects on interleukin-1β stimulated primary mice chondrocytes. Results Compared with mice receiving intragastric and intraarticular saline, mice in both intragastric and intraarticular metformin displayed attenuated articular cartilage degeneration, indicated by less cartilage damage under SEM and significantly lower OARSI scores. A higher paw withdrawal threshold and a decreased weight-bearing asymmetry were observed in the intragastric and intraarticular metformin mice compared with their corresponding saline groups in DMM model of osteoarthritis. In vitro experiments showed that metformin not only decreased the level of matrix metalloproteinase 13, but also elevated type II collagen production through activating AMPK pathway. Conclusions Metformin attenuates osteoarthritis structural worsening and modulates pain, suggesting its potential for osteoarthritis prevention or treatment.
topic Osteoarthritis
Metformin
Mice
AMPK
url http://link.springer.com/article/10.1186/s13075-020-2129-y
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