Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

MicroRNA as Possible Mediators of the Synergistic Effect of Celecoxib and Glucosamine Sulfate in Human Osteoarthritic Chondrocyte Exposed to IL-1β

Sara Cheleschi
ORCID logo ,
Nicola Veronese
* ORCID logo ,
Serafino Carta
,
Giulia Collodel
ORCID logo ,
Maria Bottaro
ORCID logo ,
Elena Moretti
ORCID logo ,
Roberta Corsaro
ORCID logo ,
Marcella Barbarino
ORCID logo ,
Antonella Fioravanti
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Version 1 : Received: 8 September 2023 / Approved: 11 September 2023 / Online: 12 September 2023 (05:43:01 CEST)

A peer-reviewed article of this Preprint also exists.

Cheleschi, S.; Veronese, N.; Carta, S.; Collodel, G.; Bottaro, M.; Moretti, E.; Corsaro, R.; Barbarino, M.; Fioravanti, A. MicroRNA as Possible Mediators of the Synergistic Effect of Celecoxib and Glucosamine Sulfate in Human Osteoarthritic Chondrocyte Exposed to IL-1β. Int. J. Mol. Sci. 2023, 24, 14994. Cheleschi, S.; Veronese, N.; Carta, S.; Collodel, G.; Bottaro, M.; Moretti, E.; Corsaro, R.; Barbarino, M.; Fioravanti, A. MicroRNA as Possible Mediators of the Synergistic Effect of Celecoxib and Glucosamine Sulfate in Human Osteoarthritic Chondrocyte Exposed to IL-1β. Int. J. Mol. Sci. 2023, 24, 14994.

Abstract

This study investigated the role of a pattern of microRNA (miRNA) as possible mediators of celecoxib and prescription-grade glucosamine sulfate (GS) effects in human osteoarthritis (OA) chondrocytes. Chondrocytes were treated with celecoxib (1.85 µM) and GS (9 µM), alone or in combination, for 24 hrs, with or without interleukin (IL)-1β (10 ng/mL). Viability was detected by MTT assay, apoptosis and reactive oxygen species (ROS) by cytometry, nitric oxide (NO) by Griess method. Gene levels of miRNA, antioxidant enzymes, nuclear factor erythroid (NRF)2, and B-cell lym-phoma (BCL)2 expressions were analyzed by quantitative real time PCR. Protein expression of NRF2 and BCL2 was also detected at immunofluorescence and western blot. Celecoxib and GS, alone or in combination, significantly increased viability, reduced apoptosis, ROS and NO production and the gene expression of miR-34a, -146a, -181a, -210, in comparison to baseline and to IL-1β. The transfection with miRNA specific inhibitors significantly counteracted the IL-1β activity and potentiated the properties of celecoxib and GS on viability, apoptosis and oxidant system, through NF-κB regulation. The observed effects were enhanced when the drugs were tested in combination. Our data confirmed the synergistic anti-inflammatory and chondroprotective properties of celecoxib and GS, suggesting miRNA as possible mediators.

Keywords

microRNA; celecoxib; glucosamine sulfate; chondrocytes; osteoarthritis; NF-κB; inflammation; chondroprotection

Subject

Medicine and Pharmacology, Medicine and Pharmacology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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