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dc.contributor.author
Siebelt, Michiel
dc.contributor.author
Korthagen, Nicoline
dc.contributor.author
Wei, Wu
dc.contributor.author
Groen, Harald
dc.contributor.author
Bastiaansen-Jenniskens, Yvonne
dc.contributor.author
Müller, Christina
dc.contributor.author
Waarsing, Jan H.
dc.contributor.author
De Jong, Marion
dc.contributor.author
Weinans, Harrie
dc.date.accessioned
2019-03-25T12:33:34Z
dc.date.available
2019-03-21T12:41:10Z
dc.date.available
2019-03-25T12:33:34Z
dc.date.issued
2015
dc.identifier.issn
1465-9905
dc.identifier.issn
1465-9913
dc.identifier.issn
1478-6362
dc.identifier.issn
1478-6354
dc.identifier.other
10.1186/s13075-015-0865-1
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/332956
dc.identifier.doi
10.3929/ethz-b-000332956
dc.description.abstract
Introduction Triamcinolone acetonide (TA) is used for osteoarthritis management to reduce pain, and pre-clinical studies have shown that TA limits osteophyte formation. Osteophyte formation is known to be facilitated by synovial macrophage activation. TA injections might influence macrophage activation and subsequently reduce osteophytosis. Although widely applied in clinical care, the mechanism through which TA exerts this effect remains unknown. In this animal study, we investigated the in vivo effects of TA injections on macrophage activation, osteophyte development and joint degeneration. Furthermore, in vitro macrophage differentiation experiments were conducted to further explain working mechanisms of TA effects found in vivo. Methods Osteoarthritis was induced in rat knees using papain injections and a running protocol. Untreated and TA-treated animals were longitudinally monitored for 12 weeks with in vivo micro–computed tomography (μCT) to measure subchondral bone changes. Synovial macrophage activation was measured in vivo using folate receptor β (FRβ)-targeted single-photon emission computed tomography/computed tomography. Articular cartilage was analyzed at 6 and 12 weeks with ex vivo contrast-enhanced μCT and histology. To further explain the outcomes of our in vivo study, TA on macrophages was also studied in vitro. These cultured macrophages were either M1- or M2-activated, and they were analyzed using fluorescence-activated cell sorting for CD163 and FRβ expression as well as for messenger RNA (mRNA) expression of interleukin (IL)-10. Results Our in vivo study showed that intra-articular injections with TA strongly enhanced FRβ+ macrophage activation. Despite stimulated macrophage activation, osteophyte formation was fully prevented. There was no beneficial effect of TA against cartilage degradation or subchondral bone sclerosis. In vitro macrophage cultures showed that TA strongly induced monocyte differentiation towards CD163+ and FRβ+ macrophages. Furthermore, TA-stimulated M2 macrophages showed enhanced IL-10 expression at the mRNA level. Conclusions TA injections potently induce a CD163+- and FRβ+-activated macrophage with anti-inflammatory characteristics such as reduced IL-10 production in vitro and lack of osteophytosis in vivo.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
BioMed Central
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Osteoarthritis
en_US
dc.subject
Triamcinolone acetonide
en_US
dc.subject
Macrophage activation
en_US
dc.subject
Cartilage degradation
en_US
dc.subject
Subchondral bone
en_US
dc.title
Triamcinolone acetonide activates an anti-inflammatory and folate receptor–positive macrophage that prevents osteophytosis in vivo
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2015-12-05
ethz.journal.title
Arthritis Research & Therapy
ethz.journal.volume
17
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
Arthritis Res Ther
ethz.pages.start
352
en_US
ethz.size
13 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03688 - Schibli, Roger / Schibli, Roger
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03688 - Schibli, Roger / Schibli, Roger
en_US
ethz.date.deposited
2019-03-21T12:41:11Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2019-03-25T12:34:00Z
ethz.rosetta.lastUpdated
2020-02-15T18:02:00Z
ethz.rosetta.versionExported
true
ethz.COinS
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