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.
Highlights
Temporomandibular joint osteoarthritis is a common condition in temporomandibular joint disorder (TMD)
The Expression of matrix metallopeptidase 13 (MMP13), MiR-140-5p, NF-κB Increased but Smad3, transforming growth factor-β 3 (TGF-β3) Downregulated in Response to IL-1β
In order to established temporomandibular joint osteoarthritis (TMJ-OA) model in vitro, mandibular condylar chondrocytes (MCCs) were induced by IL-1β (10 ng/ml) for 24 h
Summary
Temporomandibular joint osteoarthritis is a common condition in temporomandibular joint disorder (TMD). Exhibit extracellular matrix loss, condylar cartilage degradation and synovial inflammation, TMJ-OA patients often accompanied with X-ray signs in clinic (Zhao et al, 2011). Mandibular condylar cartilage contained several thick multilayers of collagen fiber zones while other articular cartilage mainly consists of hyaline cartilage (Bouvier and Zimny, 1987). Previous studies reported that highly expression of type X collagen, thickening hypertrophic layer, and bone remodeling were related to the pathological alterations of TMJ-OA (Goldring, 2012; Hashimoto et al, 2013; Zhang et al, 2013; Duan et al, 2015; Zhang J. et al, 2018). Mandibular condylar cartilage seems to be more sensitive to mechanical stress (Duan et al, 2015). What’s more, no effective targeted therapy or early prediction for TMJ-OA exists
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
