Potential Novel Prediction of TMJ-OA: MiR-140-5p Regulates Inflammation Through Smad/TGF-β Signaling
Temporomandibular joint osteoarthritis (TMJ-OA), mainly exhibit extracellular matrix loss and condylar cartilage degradation, is the most common chronic and degenerative maxillofacial osteoarthritis; however, no efficient therapy for TMJ-OA exists due to the poor understanding of its pathological pr...
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doaj-fbc228417e224f5aa915551740ee1ee62020-11-24T23:58:54ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-01-011010.3389/fphar.2019.00015434800Potential Novel Prediction of TMJ-OA: MiR-140-5p Regulates Inflammation Through Smad/TGF-β SignalingWeihao Li0Shurong Zhao1Hefeng Yang2Chao Zhang3Qiang Kang4Jie Deng5Yanhua Xu6Yu Ding7Song Li8Department of Dental Research, School of Stomatology, Kunming Medical University, Kunming, ChinaDepartment of Dental Research, School of Stomatology, Kunming Medical University, Kunming, ChinaDepartment of Dental Research, School of Stomatology, Kunming Medical University, Kunming, ChinaSchool of Public Health, Kunming Medical University, Kunming, ChinaDepartment of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, ChinaDepartment of Oral Biology and Pathology, School of Dental Medicine, Stony Brook, NY, United StatesDepartment of Dental Research, School of Stomatology, Kunming Medical University, Kunming, ChinaDepartment of Dental Research, School of Stomatology, Kunming Medical University, Kunming, ChinaDepartment of Dental Research, School of Stomatology, Kunming Medical University, Kunming, ChinaTemporomandibular joint osteoarthritis (TMJ-OA), mainly exhibit extracellular matrix loss and condylar cartilage degradation, is the most common chronic and degenerative maxillofacial osteoarthritis; however, no efficient therapy for TMJ-OA exists due to the poor understanding of its pathological progression. MicroRNA (miR)-140-5p is a novel non-coding microRNAs (miRNAs) that expressed in osteoarthritis specifically. To investigate the molecular mechanisms of miR-140-5p in TMJ-OA, primary mandibular condylar chondrocytes (MCCs) from C57BL/6N mice were treated with interleukins (IL)-1β or transfected with miR-140-5p mimics or inhibitors, respectively. The expression of matrix metallopeptidase (MMP)-13, miR-140-5p, nuclear factor (NF)-kB, Smad3 and transforming growth factor (TGF)-β3 were examined by western blotting or quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The interaction between the potential binding sequence of miR-140-5p and the 3′-untranslated region (3′UTR) of Smad3 mRNA was testified by dual-luciferase assay. Small Interfering RNA of Smad3 (Si-Smad3) was utilized to further identify the role of Smad3 mediated by miR-140-5p. The data showed MMP13, miR-140-5p and NF-kB increased significantly in response to IL-1β inflammatory response in MCCs, meanwhile, Smad3 and TGF-β3 reduced markedly. Moreover, transfection of miR-140-5p mimics significantly suppressed the expression of Smad3 and TGF-β3 in MCCs, while miR-140-5p inhibitors acted in a converse manner. As the luciferase reporter of Smad3 mRNA observed active interaction with miR-140-5p, Smad3 was identified as a direct target of miR-140-5p. Additionally, the expression of TGF-β3 was regulated upon the activation of Smad3. Together, these data suggested that miR-140-5p may play a role in regulating mandibular condylar cartilage homeostasis and potentially serve as a novel prognostic factor of TMJ-OA-like pathology.https://www.frontiersin.org/article/10.3389/fphar.2019.00015/fullmirna-140-5pTMJ-OAinflammationTGF-βSmad |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Weihao Li Shurong Zhao Hefeng Yang Chao Zhang Qiang Kang Jie Deng Yanhua Xu Yu Ding Song Li |
spellingShingle |
Weihao Li Shurong Zhao Hefeng Yang Chao Zhang Qiang Kang Jie Deng Yanhua Xu Yu Ding Song Li Potential Novel Prediction of TMJ-OA: MiR-140-5p Regulates Inflammation Through Smad/TGF-β Signaling Frontiers in Pharmacology mirna-140-5p TMJ-OA inflammation TGF-β Smad |
author_facet |
Weihao Li Shurong Zhao Hefeng Yang Chao Zhang Qiang Kang Jie Deng Yanhua Xu Yu Ding Song Li |
author_sort |
Weihao Li |
title |
Potential Novel Prediction of TMJ-OA: MiR-140-5p Regulates Inflammation Through Smad/TGF-β Signaling |
title_short |
Potential Novel Prediction of TMJ-OA: MiR-140-5p Regulates Inflammation Through Smad/TGF-β Signaling |
title_full |
Potential Novel Prediction of TMJ-OA: MiR-140-5p Regulates Inflammation Through Smad/TGF-β Signaling |
title_fullStr |
Potential Novel Prediction of TMJ-OA: MiR-140-5p Regulates Inflammation Through Smad/TGF-β Signaling |
title_full_unstemmed |
Potential Novel Prediction of TMJ-OA: MiR-140-5p Regulates Inflammation Through Smad/TGF-β Signaling |
title_sort |
potential novel prediction of tmj-oa: mir-140-5p regulates inflammation through smad/tgf-β signaling |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2019-01-01 |
description |
Temporomandibular joint osteoarthritis (TMJ-OA), mainly exhibit extracellular matrix loss and condylar cartilage degradation, is the most common chronic and degenerative maxillofacial osteoarthritis; however, no efficient therapy for TMJ-OA exists due to the poor understanding of its pathological progression. MicroRNA (miR)-140-5p is a novel non-coding microRNAs (miRNAs) that expressed in osteoarthritis specifically. To investigate the molecular mechanisms of miR-140-5p in TMJ-OA, primary mandibular condylar chondrocytes (MCCs) from C57BL/6N mice were treated with interleukins (IL)-1β or transfected with miR-140-5p mimics or inhibitors, respectively. The expression of matrix metallopeptidase (MMP)-13, miR-140-5p, nuclear factor (NF)-kB, Smad3 and transforming growth factor (TGF)-β3 were examined by western blotting or quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The interaction between the potential binding sequence of miR-140-5p and the 3′-untranslated region (3′UTR) of Smad3 mRNA was testified by dual-luciferase assay. Small Interfering RNA of Smad3 (Si-Smad3) was utilized to further identify the role of Smad3 mediated by miR-140-5p. The data showed MMP13, miR-140-5p and NF-kB increased significantly in response to IL-1β inflammatory response in MCCs, meanwhile, Smad3 and TGF-β3 reduced markedly. Moreover, transfection of miR-140-5p mimics significantly suppressed the expression of Smad3 and TGF-β3 in MCCs, while miR-140-5p inhibitors acted in a converse manner. As the luciferase reporter of Smad3 mRNA observed active interaction with miR-140-5p, Smad3 was identified as a direct target of miR-140-5p. Additionally, the expression of TGF-β3 was regulated upon the activation of Smad3. Together, these data suggested that miR-140-5p may play a role in regulating mandibular condylar cartilage homeostasis and potentially serve as a novel prognostic factor of TMJ-OA-like pathology. |
topic |
mirna-140-5p TMJ-OA inflammation TGF-β Smad |
url |
https://www.frontiersin.org/article/10.3389/fphar.2019.00015/full |
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