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miR-21 attenuated inflammation targeting MyD88 in human chondrocytes stimulated with Hyaluronan oligosaccharides.

Authors :
Scuruchi, Michele
Avenoso, Angela
Aliquò, Federica
Pantano, Alice
Campo, Giuseppe M.
Campo, Salvatore
D'Ascola, Angela
Source :
Archives of Biochemistry & Biophysics. Sep2024, Vol. 759, pN.PAG-N.PAG. 1p.
Publication Year :
2024

Abstract

Inflammation is the body's response to injuries, which depends on numerous regulatory factors. Among them, miRNAs have gained much attention for their role in regulating inflammatory gene expression at multiple levels. In particular, miR-21 is up-regulated during the inflammatory response and reported to be involved in the resolution of inflammation by down-regulating pro-inflammatory mediators, including MyD88. Herein, we evaluated the regulatory effects of miR-21 on the TLR-4/MyD88 pathway in an in vitro model of 6-mer HA oligosaccharides-induced inflammation in human chondrocytes. The exposition of chondrocytes to 6-mer HA induced the activation of the TLR4/MyD88 pathway, which culminates in NF-kB activation. Changes in miR-21, TLR-4, MyD88, NLRP3 inflammasome, IL-29, Caspase1, MMP-9, iNOS, and COX-2 mRNA expression of 6-mer HA-stimulated chondrocytes were examined by qRT-PCR. Protein amounts of TLR-4, MyD88, NLRP3 inflammasome, p -ERK1/2, p -AKT, IL-29, caspase1, MMP-9, p-NK-kB p65 subunit, and IKB-a have been evaluated by ELISA kits. NO and PGE 2 levels have been assayed by colorimetric and ELISA kits, respectively. HA oligosaccharides induced a significant increase in the expression of the above parameters, including NF-kB activity. The use of a miR-21 mimic attenuated MyD88 expression levels and the downstream effectors. On the contrary, treatment with a miR-21 inhibitor induced opposite effects. Interestingly, the use of a MyD88 siRNA confirmed MyD88 as the target of miR-21 action. Our results suggest that miR-21 expression could increase in an attempt to reduce the inflammatory response, targeting MyD88. [Display omitted] • MiR-21 is induced during 6-mer HA induced inflammation in chondrocytes. • MiR-21 regulates MyD88 expression in 6-mer HA activated chondrocytes. • MiR-21 may reduce the inflammatory response during 6-mer HA induced inflammation. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00039861
Volume :
759
Database :
Academic Search Index
Journal :
Archives of Biochemistry & Biophysics
Publication Type :
Academic Journal
Accession number :
179059996
Full Text :
https://doi.org/10.1016/j.abb.2024.110112