Cargando…

Fatty Acid Fingerprints and Hyaluronic Acid in Extracellular Vesicles from Proliferating Human Fibroblast-like Synoviocytes

Extracellular vesicles (EVs) function as conveyors of fatty acids (FAs) and other bioactive lipids and can modulate the gene expression and behavior of target cells. EV lipid composition influences the fluidity and stability of EV membranes and reflects the availability of lipid mediator precursors....

Descripción completa

Detalles Bibliográficos
Autores principales: Mustonen, Anne-Mari, Paakkonen, Tommi, Matilainen, Johanna, Rilla, Kirsi, Käkelä, Reijo, Malinen, Marjo, Takabe, Piia, Oikari, Sanna, Capra, Janne, Sihvo, Sanna P., Ryökäs, Pauliina, Nieminen, Petteri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146557/
https://www.ncbi.nlm.nih.gov/pubmed/35628422
http://dx.doi.org/10.3390/ijms23105613
_version_ 1784716592363339776
author Mustonen, Anne-Mari
Paakkonen, Tommi
Matilainen, Johanna
Rilla, Kirsi
Käkelä, Reijo
Malinen, Marjo
Takabe, Piia
Oikari, Sanna
Capra, Janne
Sihvo, Sanna P.
Ryökäs, Pauliina
Nieminen, Petteri
author_facet Mustonen, Anne-Mari
Paakkonen, Tommi
Matilainen, Johanna
Rilla, Kirsi
Käkelä, Reijo
Malinen, Marjo
Takabe, Piia
Oikari, Sanna
Capra, Janne
Sihvo, Sanna P.
Ryökäs, Pauliina
Nieminen, Petteri
author_sort Mustonen, Anne-Mari
collection PubMed
description Extracellular vesicles (EVs) function as conveyors of fatty acids (FAs) and other bioactive lipids and can modulate the gene expression and behavior of target cells. EV lipid composition influences the fluidity and stability of EV membranes and reflects the availability of lipid mediator precursors. Fibroblast-like synoviocytes (FLSs) secrete EVs that transport hyaluronic acid (HA). FLSs play a central role in inflammation, pannus formation, and cartilage degradation in joint diseases, and EVs have recently emerged as potential mediators of these effects. The aim of the present study was to follow temporal changes in HA and EV secretion by normal FLSs, and to characterize the FA profiles of FLSs and EVs during proliferation. The methods used included nanoparticle tracking analysis, confocal laser scanning microscopy, sandwich-type enzyme-linked sorbent assay, quantitative PCR, and gas chromatography. The expression of hyaluronan synthases 1–3 in FLSs and HA concentrations in conditioned media decreased during cell proliferation. This was associated with elevated proportions of 20:4n-6 and total n-6 polyunsaturated FAs (PUFAs) in high-density cells, reductions in n-3/n-6 PUFA ratios, and up-regulation of cluster of differentiation 44, tumor necrosis factor α, peroxisome proliferator-activated receptor (PPAR)-α, and PPAR-γ. Compared to the parent FLSs, 16:0, 18:0, and 18:1n-9 were enriched in the EV fraction. EV counts decreased during cell growth, and 18:2n-6 in EVs correlated with the cell count. To conclude, FLS proliferation was featured by increased 20:4n-6 proportions and reduced n-3/n-6 PUFA ratios, and FAs with a low degree of unsaturation were selectively transferred from FLSs into EVs. These FA modifications have the potential to affect membrane fluidity, biosynthesis of lipid mediators, and inflammatory processes in joints, and could eventually provide tools for translational studies to counteract cartilage degradation in inflammatory joint diseases.
format Online
Article
Text
id pubmed-9146557
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-91465572022-05-29 Fatty Acid Fingerprints and Hyaluronic Acid in Extracellular Vesicles from Proliferating Human Fibroblast-like Synoviocytes Mustonen, Anne-Mari Paakkonen, Tommi Matilainen, Johanna Rilla, Kirsi Käkelä, Reijo Malinen, Marjo Takabe, Piia Oikari, Sanna Capra, Janne Sihvo, Sanna P. Ryökäs, Pauliina Nieminen, Petteri Int J Mol Sci Article Extracellular vesicles (EVs) function as conveyors of fatty acids (FAs) and other bioactive lipids and can modulate the gene expression and behavior of target cells. EV lipid composition influences the fluidity and stability of EV membranes and reflects the availability of lipid mediator precursors. Fibroblast-like synoviocytes (FLSs) secrete EVs that transport hyaluronic acid (HA). FLSs play a central role in inflammation, pannus formation, and cartilage degradation in joint diseases, and EVs have recently emerged as potential mediators of these effects. The aim of the present study was to follow temporal changes in HA and EV secretion by normal FLSs, and to characterize the FA profiles of FLSs and EVs during proliferation. The methods used included nanoparticle tracking analysis, confocal laser scanning microscopy, sandwich-type enzyme-linked sorbent assay, quantitative PCR, and gas chromatography. The expression of hyaluronan synthases 1–3 in FLSs and HA concentrations in conditioned media decreased during cell proliferation. This was associated with elevated proportions of 20:4n-6 and total n-6 polyunsaturated FAs (PUFAs) in high-density cells, reductions in n-3/n-6 PUFA ratios, and up-regulation of cluster of differentiation 44, tumor necrosis factor α, peroxisome proliferator-activated receptor (PPAR)-α, and PPAR-γ. Compared to the parent FLSs, 16:0, 18:0, and 18:1n-9 were enriched in the EV fraction. EV counts decreased during cell growth, and 18:2n-6 in EVs correlated with the cell count. To conclude, FLS proliferation was featured by increased 20:4n-6 proportions and reduced n-3/n-6 PUFA ratios, and FAs with a low degree of unsaturation were selectively transferred from FLSs into EVs. These FA modifications have the potential to affect membrane fluidity, biosynthesis of lipid mediators, and inflammatory processes in joints, and could eventually provide tools for translational studies to counteract cartilage degradation in inflammatory joint diseases. MDPI 2022-05-17 /pmc/articles/PMC9146557/ /pubmed/35628422 http://dx.doi.org/10.3390/ijms23105613 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mustonen, Anne-Mari
Paakkonen, Tommi
Matilainen, Johanna
Rilla, Kirsi
Käkelä, Reijo
Malinen, Marjo
Takabe, Piia
Oikari, Sanna
Capra, Janne
Sihvo, Sanna P.
Ryökäs, Pauliina
Nieminen, Petteri
Fatty Acid Fingerprints and Hyaluronic Acid in Extracellular Vesicles from Proliferating Human Fibroblast-like Synoviocytes
title Fatty Acid Fingerprints and Hyaluronic Acid in Extracellular Vesicles from Proliferating Human Fibroblast-like Synoviocytes
title_full Fatty Acid Fingerprints and Hyaluronic Acid in Extracellular Vesicles from Proliferating Human Fibroblast-like Synoviocytes
title_fullStr Fatty Acid Fingerprints and Hyaluronic Acid in Extracellular Vesicles from Proliferating Human Fibroblast-like Synoviocytes
title_full_unstemmed Fatty Acid Fingerprints and Hyaluronic Acid in Extracellular Vesicles from Proliferating Human Fibroblast-like Synoviocytes
title_short Fatty Acid Fingerprints and Hyaluronic Acid in Extracellular Vesicles from Proliferating Human Fibroblast-like Synoviocytes
title_sort fatty acid fingerprints and hyaluronic acid in extracellular vesicles from proliferating human fibroblast-like synoviocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146557/
https://www.ncbi.nlm.nih.gov/pubmed/35628422
http://dx.doi.org/10.3390/ijms23105613
work_keys_str_mv AT mustonenannemari fattyacidfingerprintsandhyaluronicacidinextracellularvesiclesfromproliferatinghumanfibroblastlikesynoviocytes
AT paakkonentommi fattyacidfingerprintsandhyaluronicacidinextracellularvesiclesfromproliferatinghumanfibroblastlikesynoviocytes
AT matilainenjohanna fattyacidfingerprintsandhyaluronicacidinextracellularvesiclesfromproliferatinghumanfibroblastlikesynoviocytes
AT rillakirsi fattyacidfingerprintsandhyaluronicacidinextracellularvesiclesfromproliferatinghumanfibroblastlikesynoviocytes
AT kakelareijo fattyacidfingerprintsandhyaluronicacidinextracellularvesiclesfromproliferatinghumanfibroblastlikesynoviocytes
AT malinenmarjo fattyacidfingerprintsandhyaluronicacidinextracellularvesiclesfromproliferatinghumanfibroblastlikesynoviocytes
AT takabepiia fattyacidfingerprintsandhyaluronicacidinextracellularvesiclesfromproliferatinghumanfibroblastlikesynoviocytes
AT oikarisanna fattyacidfingerprintsandhyaluronicacidinextracellularvesiclesfromproliferatinghumanfibroblastlikesynoviocytes
AT caprajanne fattyacidfingerprintsandhyaluronicacidinextracellularvesiclesfromproliferatinghumanfibroblastlikesynoviocytes
AT sihvosannap fattyacidfingerprintsandhyaluronicacidinextracellularvesiclesfromproliferatinghumanfibroblastlikesynoviocytes
AT ryokaspauliina fattyacidfingerprintsandhyaluronicacidinextracellularvesiclesfromproliferatinghumanfibroblastlikesynoviocytes
AT nieminenpetteri fattyacidfingerprintsandhyaluronicacidinextracellularvesiclesfromproliferatinghumanfibroblastlikesynoviocytes