Timing Expression of miR203a-3p during OA Disease: Preliminary In Vitro Evidence
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Published:2023-02-21
Issue:5
Volume:24
Page:4316
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Costa Viviana1ORCID, De Fine Marcello2, Raimondi Lavinia1ORCID, Bellavia Daniele1ORCID, Cordaro Aurora1, Carina Valeria1, Alessandro Riccardo34ORCID, Pignatti Giovanni2, Fini Milena5, Giavaresi Gianluca1ORCID, De Luca Angela1ORCID
Affiliation:
1. Scienze e Tecnologie Chirurgiche, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy 2. Ortopedia Generale, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy 3. Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), Section of Biology and Genetics, University of Palermo, 90133 Palermo, Italy 4. Istituto per la Ricerca e l’Innovazione Biomedica (IRIB), 90146 Palermo, Italy 5. Direzione Scientifica, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
Abstract
Osteoarthritis (OA) is a degenerative bone disease that involves the microenvironment and macroenvironment of joints. Progressive joint tissue degradation and loss of extracellular matrix elements, together with different grades of inflammation, are important hallmarks of OA disease. Therefore, the identification of specific biomarkers to distinguish the stages of disease becomes a primary necessity in clinical practice. To this aim, we investigated the role of miR203a-3p in OA progression starting from the evidence obtained by osteoblasts isolated from joint tissues of OA patients classified according to different Kellgren and Lawrence (KL) grading (KL ≤ 3 and KL > 3) and hMSCs treated with IL-1β. Through qRT-PCR analysis, it was found that osteoblasts (OBs) derived from the KL ≤ 3 group expressed high levels of miR203a-3p and low levels of ILs compared with those of OBs derived from the KL > 3 group. The stimulation with IL-1β improved the expression of miR203a-3p and the methylation of the IL-6 promoter gene, favoring an increase in relative protein expression. The gain and loss of function studies showed that the transfection with miR203a-3p inhibitor alone or in co-treatments with IL-1β was able to induce the expression of CX-43 and SP-1 and to modulate the expression of TAZ, in OBs derived from OA patients with KL ≤ 3 compared with KL > 3. These events, confirmed also by qRT-PCR analysis, Western blot, and ELISA assay performed on hMSCs stimulated with IL-1β, supported our hypothesis about the role of miR203a-3p in OA progression. The results suggested that during the early stage, miR203a-3p displayed a protective role reducing the inflammatory effects on CX-43, SP-1, and TAZ. During the OA progression the downregulation of miR203a-3p and consequently the upregulation of CX-43/SP-1 and TAZ expression improved the inflammatory response and the reorganization of the cytoskeleton. This role led to the subsequent stage of the disease, where the aberrant inflammatory and fibrotic responses determined the destruction of the joint.
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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