Triamcinolone acetonide activates an anti-inflammatory and folate receptor–positive macrophage that prevents osteophytosis in vivo
OPEN ACCESS
Author / Producer
Date
2015
Publication Type
Journal Article
ETH Bibliography
yes
Citations
Altmetric
OPEN ACCESS
Data
Rights / License
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.
Permanent link
Publication status
published
External links
Editor
Book title
Journal / series
Volume
17 (1)
Pages / Article No.
352
Publisher
BioMed Central
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
Osteoarthritis; Triamcinolone acetonide; Macrophage activation; Cartilage degradation; Subchondral bone
Organisational unit
03688 - Schibli, Roger / Schibli, Roger