In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 12 ( 2022-12-28), p. e0267921-
Abstract:
Synovial fluid is composed of hyaluronan and proteoglycan-4 (PRG4 or lubricin), which work synergistically to maintain joint lubrication. In diseases like osteoarthritis, hyaluronan and PRG4 concentrations can be altered, resulting in lowered synovial fluid viscosity, and pro-inflammatory cytokine concentrations within the synovial fluid increase. Synovial fibroblasts within the synovium are responsible for contributing to synovial fluid and can be targeted to improve endogenous production of hyaluronan and PRG4 and to alter the cytokine profile. We cyclically loaded SW982 synoviocytes to 0%, 5%, 10%, or 20% strain for three hours at 1 Hz. To assess the impact of substrate stiffness, we compared the 0% strain group to cells grown on tissue culture plastic. We measured the expression of hyaluronan turnover genes, hyaluronan localization within the cell layer, hyaluronan concentration, PRG4 concentration, and the cytokine profile within the media. Our results show that the addition of cyclic loading increased HAS3 expression, but not in a magnitude-dependent response. Hyaluronidase expression was impacted by strain magnitude, which is exemplified by the decrease in hyaluronan concentration due to cyclic loading. We also show that PRG4 concentration is increased at 5% strain, while higher strain magnitude decreases overall PRG4 concentration. Finally, 10% and 20% strain show a distinct, more pro-inflammatory cytokine profile when compared to the unloaded group. Multivariate analysis showed distinct separation between certain strain groups in being able to predict strain group, hyaluronan concentration, and PRG4 concentration from gene expression or cytokine concentration data, highlighting the complexity of the system. Overall, this study shows that cyclic loading can be used tool to modulate the endogenous production of hyaluronan, PRG4, and cytokines from synovial fibroblasts.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0267921
DOI:
10.1371/journal.pone.0267921.g001
DOI:
10.1371/journal.pone.0267921.g002
DOI:
10.1371/journal.pone.0267921.g003
DOI:
10.1371/journal.pone.0267921.g004
DOI:
10.1371/journal.pone.0267921.g005
DOI:
10.1371/journal.pone.0267921.g006
DOI:
10.1371/journal.pone.0267921.g007
DOI:
10.1371/journal.pone.0267921.s001
DOI:
10.1371/journal.pone.0267921.s002
DOI:
10.1371/journal.pone.0267921.s003
DOI:
10.1371/journal.pone.0267921.s004
DOI:
10.1371/journal.pone.0267921.s005
DOI:
10.1371/journal.pone.0267921.s006
DOI:
10.1371/journal.pone.0267921.s007
DOI:
10.1371/journal.pone.0267921.s008
DOI:
10.1371/journal.pone.0267921.s009
DOI:
10.1371/journal.pone.0267921.s010
DOI:
10.1371/journal.pone.0267921.s011
DOI:
10.1371/journal.pone.0267921.r001
DOI:
10.1371/journal.pone.0267921.r002
DOI:
10.1371/journal.pone.0267921.r003
DOI:
10.1371/journal.pone.0267921.r004
DOI:
10.1371/journal.pone.0267921.r005
DOI:
10.1371/journal.pone.0267921.r006
DOI:
10.1371/journal.pone.0267921.r007
DOI:
10.1371/journal.pone.0267921.r008
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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