Characterization of hyaluronan-coated extracellular vesicles in synovial fluid of patients with osteoarthritis and rheumatoid arthritis.
Extracellular vesicles
Hyaluronan
Osteoarthritis
Rheumatoid arthritis
Synovial fluid
Journal
BMC musculoskeletal disorders
ISSN: 1471-2474
Titre abrégé: BMC Musculoskelet Disord
Pays: England
ID NLM: 100968565
Informations de publication
Date de publication:
06 Mar 2021
06 Mar 2021
Historique:
received:
29
06
2020
accepted:
24
02
2021
entrez:
7
3
2021
pubmed:
8
3
2021
medline:
15
5
2021
Statut:
epublish
Résumé
Hyaluronic acid (HA) is the major extracellular matrix glycosaminoglycan with a reduced synovial fluid (SF) concentration in arthropathies. Cell-derived extracellular vesicles (EV) have also been proposed to contribute to pathogenesis in joint diseases. It has recently been shown that human SF contains HA-coated EV (HA-EV), but their concentration and function in joint pathologies remain unknown. The aim of the present study was to develop an applicable method based on confocal laser scanning microscopy (CLSM) and image analysis for the quantification of EV, HA-particles, and HA-EV in the SF of the human knee joint. Samples were collected during total knee replacement surgery from patients with end-stage rheumatoid arthritis (RA, n = 8) and osteoarthritis (OA, n = 8), or during diagnostic/therapeutic arthroscopy unrelated to OA/RA (control, n = 7). To characterize and quantify EV, HA-particles, and HA-EV, SF was double-stained with plasma membrane and HA probes and visualized by CLSM. Comparisons between the patient groups were performed with the Kruskal-Wallis analysis of variance. The size distribution of EV and HA-particles was mostly similar in the study groups. Approximately 66% of EV fluorescence was co-localized with HA verifying that a significant proportion of EV carry HA. The study groups were clearly separated by the discriminant analysis based on the CLSM data. The intensities of EV and HA-particle fluorescences were lower in the RA than in the control and OA groups. CLSM analysis offers a useful tool to assess HA-EV in SF samples. The altered EV and HA intensities in the RA SF could have possible implications for diagnostics and therapy.
Sections du résumé
BACKGROUND
BACKGROUND
Hyaluronic acid (HA) is the major extracellular matrix glycosaminoglycan with a reduced synovial fluid (SF) concentration in arthropathies. Cell-derived extracellular vesicles (EV) have also been proposed to contribute to pathogenesis in joint diseases. It has recently been shown that human SF contains HA-coated EV (HA-EV), but their concentration and function in joint pathologies remain unknown.
METHODS
METHODS
The aim of the present study was to develop an applicable method based on confocal laser scanning microscopy (CLSM) and image analysis for the quantification of EV, HA-particles, and HA-EV in the SF of the human knee joint. Samples were collected during total knee replacement surgery from patients with end-stage rheumatoid arthritis (RA, n = 8) and osteoarthritis (OA, n = 8), or during diagnostic/therapeutic arthroscopy unrelated to OA/RA (control, n = 7). To characterize and quantify EV, HA-particles, and HA-EV, SF was double-stained with plasma membrane and HA probes and visualized by CLSM. Comparisons between the patient groups were performed with the Kruskal-Wallis analysis of variance.
RESULTS
RESULTS
The size distribution of EV and HA-particles was mostly similar in the study groups. Approximately 66% of EV fluorescence was co-localized with HA verifying that a significant proportion of EV carry HA. The study groups were clearly separated by the discriminant analysis based on the CLSM data. The intensities of EV and HA-particle fluorescences were lower in the RA than in the control and OA groups.
CONCLUSIONS
CONCLUSIONS
CLSM analysis offers a useful tool to assess HA-EV in SF samples. The altered EV and HA intensities in the RA SF could have possible implications for diagnostics and therapy.
Identifiants
pubmed: 33676459
doi: 10.1186/s12891-021-04115-w
pii: 10.1186/s12891-021-04115-w
pmc: PMC7937210
doi:
Substances chimiques
Hyaluronic Acid
9004-61-9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
247Subventions
Organisme : Jane ja Aatos Erkon Säätiö
ID : n/a
Organisme : Terveyden Tutkimuksen Toimikunta
ID : #276426
Organisme : Terveyden Tutkimuksen Toimikunta
ID : #284520
Organisme : Terveyden Tutkimuksen Toimikunta
ID : #312519
Organisme : Terveyden Tutkimuksen Toimikunta
ID : #322429
Références
Arthritis Res Ther. 2004;6(6):R514-20
pubmed: 15535829
Arthritis Rheum. 2002 Nov;46(11):2857-66
pubmed: 12428225
Rheumatol Ther. 2014 Dec;1(1):45-54
pubmed: 27747759
Arthritis Res Ther. 2009;11(2):R40
pubmed: 19291304
Microsc Microanal. 2014 Jun;20(3):903-11
pubmed: 24641871
Interdiscip Toxicol. 2013 Sep;6(3):111-25
pubmed: 24678248
Nat Rev Rheumatol. 2010 Jan;6(1):21-9
pubmed: 19949432
J Histochem Cytochem. 2008 Oct;56(10):901-10
pubmed: 18574248
Science. 2010 Jan 29;327(5965):580-3
pubmed: 20110505
Clin Chim Acta. 1989 May 31;181(3):317-23
pubmed: 2474393
Biorheology. 2007;44(2):59-74
pubmed: 17538199
Matrix Biol. 2017 Dec;64:54-68
pubmed: 28483644
Ann Rheum Dis. 1995 May;54(5):408-12
pubmed: 7794051
Histochem Cell Biol. 2000 Apr;113(4):265-77
pubmed: 10857478
Arthritis Rheum. 2002 Jun;46(6):1498-503
pubmed: 12115179
Cancer Res. 2002 Nov 15;62(22):6410-3
pubmed: 12438225
Biotechnol J. 2019 Jan;14(1):e1700716
pubmed: 29878510
J Orthop Res. 1999 Nov;17(6):858-69
pubmed: 10632453
Clin Chim Acta. 2014 Jun 10;433:20-7
pubmed: 24607326
PLoS One. 2012;7(11):e49726
pubmed: 23185418
Immunity. 2017 Feb 21;46(2):183-196
pubmed: 28228278
Cartilage. 2019 Jan;10(1):43-52
pubmed: 29429372
Osteoarthritis Cartilage. 2012 Dec;20(12):1484-99
pubmed: 22960092
Int J Cell Biol. 2015;2015:745237
pubmed: 26448758
Clin Transl Med. 2018 Feb 16;7(1):6
pubmed: 29450666
PLoS One. 2015 May 01;10(5):e0125192
pubmed: 25933137
Matrix Biol. 2019 Jan;75-76:201-219
pubmed: 29066152
Biol Sex Differ. 2015 May 11;6:10
pubmed: 25964851
Exp Cell Res. 2013 Aug 1;319(13):2006-2018
pubmed: 23732660
J Orthop Res. 2016 Nov;34(11):1960-1968
pubmed: 26919117
Arthritis Rheum. 2004 Feb;50(2):516-25
pubmed: 14872494
Mod Rheumatol. 2009;19(3):265-72
pubmed: 19337689
Mol Immunol. 2018 Jan;93:125-132
pubmed: 29175592
J Extracell Vesicles. 2018 Nov 23;7(1):1535750
pubmed: 30637094
Adv Cancer Res. 2014;123:121-48
pubmed: 25081528
Arthritis Rheum. 1993 Feb;36(2):247-53
pubmed: 8431214
Arthritis Res Ther. 2009;11(5):R156
pubmed: 19832990
Arthritis Res Ther. 2016 Dec 1;18(1):286
pubmed: 27906035
Immunol Res. 2014 May;58(2-3):186-92
pubmed: 24614953
J Extracell Vesicles. 2013 May 27;2:
pubmed: 24009894
Blood. 2011 Jan 27;117(4):e39-48
pubmed: 21041717
J Bone Joint Surg Am. 2012 May 16;94(10):e64
pubmed: 22617930
J Extracell Vesicles. 2018 Jun 26;7(1):1490145
pubmed: 29963299
Cell Mol Life Sci. 2011 Aug;68(16):2667-88
pubmed: 21560073
Am J Respir Crit Care Med. 2005 Jul 1;172(1):92-8
pubmed: 15790861
J Rheumatol. 2014 May;41(5):945-54
pubmed: 24737908
Matrix Biol. 2017 Nov;63:38-54
pubmed: 28043889
Clin Exp Immunol. 2015 Jun;180(3):442-51
pubmed: 25639560
Exp Cell Res. 2011 Feb 15;317(4):383-91
pubmed: 21134368