The role of microRNA-3085 in chondrocyte function

Abstract MicroRNAs have been shown to play a role in cartilage development, homeostasis and breakdown during osteoarthritis. We previously identified miR-3085 in humans as a chondrocyte-selective microRNA, however it could not be detected by Northern blot. The aim of the current study was to prove t...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Linh Le, Lingzi Niu, Matthew J. Barter, David A. Young, Tamas Dalmay, Ian M. Clark, Tracey E. Swingler
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cfc83db974f44c4a99653de7ef60af7c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:cfc83db974f44c4a99653de7ef60af7c
record_format	dspace
spelling	oai:doaj.org-article:cfc83db974f44c4a99653de7ef60af7c2021-12-02T12:03:14ZThe role of microRNA-3085 in chondrocyte function10.1038/s41598-020-78606-62045-2322https://doaj.org/article/cfc83db974f44c4a99653de7ef60af7c2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78606-6https://doaj.org/toc/2045-2322Abstract MicroRNAs have been shown to play a role in cartilage development, homeostasis and breakdown during osteoarthritis. We previously identified miR-3085 in humans as a chondrocyte-selective microRNA, however it could not be detected by Northern blot. The aim of the current study was to prove that miR-3085 is a microRNA and to investigate the function of miR-3085 in signaling pathways relevant to cartilage homeostasis and osteoarthritis. Here, we confirm that miR-3085 is a microRNA and not another class of small RNA using (1) a pre-miR hairpin maturation assay, (2) expression levels in a Dicer null cell line, and (3) Ago2 pulldown. MicroRNA-3085-3p is expressed more highly in micromass than monolayer cultured chondrocytes. Transfection of miR-3085-3p into chondrocytes decreases expression of COL2A1 and ACAN, both of which are validated as direct targets of miR-3085-3p. Interleukin-1 induces the expression of miR-3085-3p, at least in part via NFκB. In a feed-forward mechanism, miR-3085-3p then potentiates NFκB signaling. However, at early time points after transfection, its action appears to be inhibitory. MyD88 has been shown to be a direct target of miR-3085-3p and may be responsible for the early inhibition of NFκB signaling. However, at later time points, MyD88 knockdown remains inhibitory and so other functions of miR-3085-3p are clearly dominant. TGFβ1 also induces the expression of miR-3085-3p, but in this instance, it exerts a feedback inhibition on signaling with SMAD3 and SMAD4 shown to be direct targets. This in vitro analysis shows that miR-3085-3p functions in chondrocytes to induce IL-1-signaling, reduce TGFβ1 signaling, and inhibit expression of matrix genes. These data suggest that miR-3085-3p has a role in chondrocyte function and could contribute to the process of osteoarthritis.Linh LeLingzi NiuMatthew J. BarterDavid A. YoungTamas DalmayIan M. ClarkTracey E. SwinglerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Linh Le Lingzi Niu Matthew J. Barter David A. Young Tamas Dalmay Ian M. Clark Tracey E. Swingler The role of microRNA-3085 in chondrocyte function
description	Abstract MicroRNAs have been shown to play a role in cartilage development, homeostasis and breakdown during osteoarthritis. We previously identified miR-3085 in humans as a chondrocyte-selective microRNA, however it could not be detected by Northern blot. The aim of the current study was to prove that miR-3085 is a microRNA and to investigate the function of miR-3085 in signaling pathways relevant to cartilage homeostasis and osteoarthritis. Here, we confirm that miR-3085 is a microRNA and not another class of small RNA using (1) a pre-miR hairpin maturation assay, (2) expression levels in a Dicer null cell line, and (3) Ago2 pulldown. MicroRNA-3085-3p is expressed more highly in micromass than monolayer cultured chondrocytes. Transfection of miR-3085-3p into chondrocytes decreases expression of COL2A1 and ACAN, both of which are validated as direct targets of miR-3085-3p. Interleukin-1 induces the expression of miR-3085-3p, at least in part via NFκB. In a feed-forward mechanism, miR-3085-3p then potentiates NFκB signaling. However, at early time points after transfection, its action appears to be inhibitory. MyD88 has been shown to be a direct target of miR-3085-3p and may be responsible for the early inhibition of NFκB signaling. However, at later time points, MyD88 knockdown remains inhibitory and so other functions of miR-3085-3p are clearly dominant. TGFβ1 also induces the expression of miR-3085-3p, but in this instance, it exerts a feedback inhibition on signaling with SMAD3 and SMAD4 shown to be direct targets. This in vitro analysis shows that miR-3085-3p functions in chondrocytes to induce IL-1-signaling, reduce TGFβ1 signaling, and inhibit expression of matrix genes. These data suggest that miR-3085-3p has a role in chondrocyte function and could contribute to the process of osteoarthritis.
format	article
author	Linh Le Lingzi Niu Matthew J. Barter David A. Young Tamas Dalmay Ian M. Clark Tracey E. Swingler
author_facet	Linh Le Lingzi Niu Matthew J. Barter David A. Young Tamas Dalmay Ian M. Clark Tracey E. Swingler
author_sort	Linh Le
title	The role of microRNA-3085 in chondrocyte function
title_short	The role of microRNA-3085 in chondrocyte function
title_full	The role of microRNA-3085 in chondrocyte function
title_fullStr	The role of microRNA-3085 in chondrocyte function
title_full_unstemmed	The role of microRNA-3085 in chondrocyte function
title_sort	role of microrna-3085 in chondrocyte function
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/cfc83db974f44c4a99653de7ef60af7c
work_keys_str_mv	AT linhle theroleofmicrorna3085inchondrocytefunction AT lingziniu theroleofmicrorna3085inchondrocytefunction AT matthewjbarter theroleofmicrorna3085inchondrocytefunction AT davidayoung theroleofmicrorna3085inchondrocytefunction AT tamasdalmay theroleofmicrorna3085inchondrocytefunction AT ianmclark theroleofmicrorna3085inchondrocytefunction AT traceyeswingler theroleofmicrorna3085inchondrocytefunction AT linhle roleofmicrorna3085inchondrocytefunction AT lingziniu roleofmicrorna3085inchondrocytefunction AT matthewjbarter roleofmicrorna3085inchondrocytefunction AT davidayoung roleofmicrorna3085inchondrocytefunction AT tamasdalmay roleofmicrorna3085inchondrocytefunction AT ianmclark roleofmicrorna3085inchondrocytefunction AT traceyeswingler roleofmicrorna3085inchondrocytefunction
_version_	1718394775577559040

The role of microRNA-3085 in chondrocyte function

Ejemplares similares