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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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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