Metformin Exhibits Anti‐Inflammatory Effects by Regulating microRNA‐451/CXCL16 and B Cell Leukemia/Lymphoma 2 in Patients With Osteoarthritis

Objective Osteoarthritis (OA) is the most common cause of chronic disability in joints among older individuals. The primary goal of OA treatment is pain relief to improve the quality of life. Inflammation and aging are involved in the pathogenesis of pain in OA. In this study, we evaluated the abili...

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Main Authors: Nahid Alimoradi, Amin Ramezani, Mohammad Tahami, Negar Firouzabadi
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:ACR Open Rheumatology
Online Access:https://doi.org/10.1002/acr2.11755
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author Nahid Alimoradi
Amin Ramezani
Mohammad Tahami
Negar Firouzabadi
author_facet Nahid Alimoradi
Amin Ramezani
Mohammad Tahami
Negar Firouzabadi
author_sort Nahid Alimoradi
collection DOAJ
description Objective Osteoarthritis (OA) is the most common cause of chronic disability in joints among older individuals. The primary goal of OA treatment is pain relief to improve the quality of life. Inflammation and aging are involved in the pathogenesis of pain in OA. In this study, we evaluated the ability of metformin to regulate microRNAs, such as miR‐451 and miR‐15b, and their target proteins, CXCL16 and B cell leukemia/lymphoma 2 (BCL‐2), involved in inflammation and apoptosis. Methods In this double‐blind placebo‐controlled clinical trial, patients were randomly divided into two groups: one receiving metformin and the other receiving a placebo for four months (starting at 0.5 g/day for the first week, increasing to 1 g/day for the second week, and increasing to 1.5 g/day for the remaining period). In addition to evaluating the clinical response using the Knee Injury and Osteoarthritis Outcome Score questionnaire, miR‐451 and miR‐15b expression levels were detected using real‐time polymerase chain reaction. The serum levels of CXCL16 and BCL‐2 were evaluated using enzyme‐linked immunosorbent assay kits before (time zero) and after treatment (month four). Results Metformin increased miR‐451 expression levels simultaneously with pain reduction, whereas miR‐15b expression did not change significantly after four months of treatment. Also, metformin decreased the serum levels of BCL‐2 and CXCL16 in patients with OA. Conclusion The effects of metformin in reducing pain can be attributed to many factors, including its anti‐inflammatory and antiaging effects. Our findings suggest that metformin may reduce pain and inflammation in patients with OA through the regulation of miR‐451/CXCL16 and BCL‐2.
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spelling doaj-art-68520bca86524b8d9dd4f06c9edfa1112025-02-04T06:21:23ZengWileyACR Open Rheumatology2578-57452025-01-0171n/an/a10.1002/acr2.11755Metformin Exhibits Anti‐Inflammatory Effects by Regulating microRNA‐451/CXCL16 and B Cell Leukemia/Lymphoma 2 in Patients With OsteoarthritisNahid Alimoradi0Amin Ramezani1Mohammad Tahami2Negar Firouzabadi3Shiraz University of Medical Sciences Shiraz IranShiraz University of Medical Sciences Shiraz IranShiraz University of Medical Sciences Shiraz IranShiraz University of Medical Sciences Shiraz IranObjective Osteoarthritis (OA) is the most common cause of chronic disability in joints among older individuals. The primary goal of OA treatment is pain relief to improve the quality of life. Inflammation and aging are involved in the pathogenesis of pain in OA. In this study, we evaluated the ability of metformin to regulate microRNAs, such as miR‐451 and miR‐15b, and their target proteins, CXCL16 and B cell leukemia/lymphoma 2 (BCL‐2), involved in inflammation and apoptosis. Methods In this double‐blind placebo‐controlled clinical trial, patients were randomly divided into two groups: one receiving metformin and the other receiving a placebo for four months (starting at 0.5 g/day for the first week, increasing to 1 g/day for the second week, and increasing to 1.5 g/day for the remaining period). In addition to evaluating the clinical response using the Knee Injury and Osteoarthritis Outcome Score questionnaire, miR‐451 and miR‐15b expression levels were detected using real‐time polymerase chain reaction. The serum levels of CXCL16 and BCL‐2 were evaluated using enzyme‐linked immunosorbent assay kits before (time zero) and after treatment (month four). Results Metformin increased miR‐451 expression levels simultaneously with pain reduction, whereas miR‐15b expression did not change significantly after four months of treatment. Also, metformin decreased the serum levels of BCL‐2 and CXCL16 in patients with OA. Conclusion The effects of metformin in reducing pain can be attributed to many factors, including its anti‐inflammatory and antiaging effects. Our findings suggest that metformin may reduce pain and inflammation in patients with OA through the regulation of miR‐451/CXCL16 and BCL‐2.https://doi.org/10.1002/acr2.11755
spellingShingle Nahid Alimoradi
Amin Ramezani
Mohammad Tahami
Negar Firouzabadi
Metformin Exhibits Anti‐Inflammatory Effects by Regulating microRNA‐451/CXCL16 and B Cell Leukemia/Lymphoma 2 in Patients With Osteoarthritis
ACR Open Rheumatology
title Metformin Exhibits Anti‐Inflammatory Effects by Regulating microRNA‐451/CXCL16 and B Cell Leukemia/Lymphoma 2 in Patients With Osteoarthritis
title_full Metformin Exhibits Anti‐Inflammatory Effects by Regulating microRNA‐451/CXCL16 and B Cell Leukemia/Lymphoma 2 in Patients With Osteoarthritis
title_fullStr Metformin Exhibits Anti‐Inflammatory Effects by Regulating microRNA‐451/CXCL16 and B Cell Leukemia/Lymphoma 2 in Patients With Osteoarthritis
title_full_unstemmed Metformin Exhibits Anti‐Inflammatory Effects by Regulating microRNA‐451/CXCL16 and B Cell Leukemia/Lymphoma 2 in Patients With Osteoarthritis
title_short Metformin Exhibits Anti‐Inflammatory Effects by Regulating microRNA‐451/CXCL16 and B Cell Leukemia/Lymphoma 2 in Patients With Osteoarthritis
title_sort metformin exhibits anti inflammatory effects by regulating microrna 451 cxcl16 and b cell leukemia lymphoma 2 in patients with osteoarthritis
url https://doi.org/10.1002/acr2.11755
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AT aminramezani metforminexhibitsantiinflammatoryeffectsbyregulatingmicrorna451cxcl16andbcellleukemialymphoma2inpatientswithosteoarthritis
AT mohammadtahami metforminexhibitsantiinflammatoryeffectsbyregulatingmicrorna451cxcl16andbcellleukemialymphoma2inpatientswithosteoarthritis
AT negarfirouzabadi metforminexhibitsantiinflammatoryeffectsbyregulatingmicrorna451cxcl16andbcellleukemialymphoma2inpatientswithosteoarthritis