{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:29:21Z","timestamp":1790627361925,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Academy of Finland","award":["276426"],"award-info":[{"award-number":["276426"]}]},{"name":"Academy of Finland","award":["284520"],"award-info":[{"award-number":["284520"]}]},{"name":"Academy of Finland","award":["312519"],"award-info":[{"award-number":["312519"]}]},{"name":"Academy of Finland","award":["322429"],"award-info":[{"award-number":["322429"]}]},{"name":"Jane and Aatos Erkko Foundation","award":["276426"],"award-info":[{"award-number":["276426"]}]},{"name":"Jane and Aatos Erkko Foundation","award":["284520"],"award-info":[{"award-number":["284520"]}]},{"name":"Jane and Aatos Erkko Foundation","award":["312519"],"award-info":[{"award-number":["312519"]}]},{"name":"Jane and Aatos Erkko Foundation","award":["322429"],"award-info":[{"award-number":["322429"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u20133 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 \u03b1, peroxisome proliferator-activated receptor (PPAR)-\u03b1, and PPAR-\u03b3. 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.<\/jats:p>","DOI":"10.3390\/ijms23105613","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T08:34:29Z","timestamp":1652776469000},"page":"5613","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Fatty Acid Fingerprints and Hyaluronic Acid in Extracellular Vesicles from Proliferating Human Fibroblast-like Synoviocytes"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2266-2518","authenticated-orcid":false,"given":"Anne-Mari","family":"Mustonen","sequence":"first","affiliation":[{"name":"Institute of Biomedicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland"},{"name":"Department of Environmental and Biological Sciences, Faculty of Science and Forestry, University of Eastern Finland, P.O. Box 111, FI-80101 Joensuu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommi","family":"Paakkonen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7239-2128","authenticated-orcid":false,"given":"Johanna","family":"Matilainen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7862-5727","authenticated-orcid":false,"given":"Kirsi","family":"Rilla","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reijo","family":"K\u00e4kel\u00e4","sequence":"additional","affiliation":[{"name":"Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, P.O. Box 65, FI-00014 Helsinki, Finland"},{"name":"Helsinki University Lipidomics Unit (HiLIPID), Helsinki Institute of Life Science (HiLIFE) and Biocenter Finland, P.O. Box 65, FI-00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjo","family":"Malinen","sequence":"additional","affiliation":[{"name":"Department of Environmental and Biological Sciences, Faculty of Science and Forestry, University of Eastern Finland, P.O. Box 111, FI-80101 Joensuu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piia","family":"Takabe","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanna","family":"Oikari","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8446-2357","authenticated-orcid":false,"given":"Janne","family":"Capra","sequence":"additional","affiliation":[{"name":"Cell and Tissue Imaging Unit, Institute of Biomedicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanna P.","family":"Sihvo","sequence":"additional","affiliation":[{"name":"Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, P.O. Box 65, FI-00014 Helsinki, Finland"},{"name":"Helsinki University Lipidomics Unit (HiLIPID), Helsinki Institute of Life Science (HiLIFE) and Biocenter Finland, P.O. 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