Triamcinolone acetonide activates an anti-inflammatory and folate
receptor-positive macrophage that prevents osteophytosis in vivo
#MMPMID26637220
Siebelt M
; Korthagen N
; Wei W
; Groen H
; Bastiaansen-Jenniskens Y
; Müller C
; Waarsing JH
; de Jong M
; Weinans H
Arthritis Res Ther
2015[Dec]; 17
(?): 352
PMID26637220
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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
(?CT) to measure subchondral bone changes. Synovial macrophage activation was
measured in vivo using folate receptor ? (FR?)-targeted single-photon emission
computed tomography/computed tomography. Articular cartilage was analyzed at 6
and 12 weeks with ex vivo contrast-enhanced ?CT 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 FR? 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 FR?(+) 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 FR?(+) macrophages. Furthermore, TA-stimulated M2 macrophages showed
enhanced IL-10 expression at the mRNA level. CONCLUSIONS: TA injections potently
induce a CD163(+)- and FR?(+)-activated macrophage with anti-inflammatory
characteristics such as reduced IL-10 production in vitro and lack of
osteophytosis in vivo.
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