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  • Title: Potential Novel Prediction of TMJ-OA: MiR-140-5p Regulates Inflammation Through Smad/TGF-β Signaling.
    Author: Li W, Zhao S, Yang H, Zhang C, Kang Q, Deng J, Xu Y, Ding Y, Li S.
    Journal: Front Pharmacol; 2019; 10():15. PubMed ID: 30728776.
    Abstract:
    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.
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