Timing Expression of miR203a-3p during OA Disease: Preliminary In Vitro Evidence.
CX-43
SP-1
TAZ
interleukines
microRNAs
osteoarthritis
osteoblasts
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
21 Feb 2023
21 Feb 2023
Historique:
received:
25
11
2022
revised:
12
01
2023
accepted:
17
02
2023
entrez:
11
3
2023
pubmed:
12
3
2023
medline:
15
3
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36901745
pii: ijms24054316
doi: 10.3390/ijms24054316
pmc: PMC10002134
pii:
doi:
Substances chimiques
Interleukin-1beta
0
MicroRNAs
0
MIRN203 microRNA, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Fondi 5 per mille ANNO 2020- 2020/730443 "Identificazione di miRNAs associati alla differenza di genere in pazienti affetti da OA" MIR.G.OA.
ID : Fondi 5 per mille ANNO 2020- 2020/730443
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