![]() 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. Furthermore, TA-stimulated M2 macrophages showed enhanced IL-10 expression at the mRNA level. ![]() ![]() In vitro macrophage cultures showed that TA strongly induced monocyte differentiation towards CD163 + and FRβ + macrophages. There was no beneficial effect of TA against cartilage degradation or subchondral bone sclerosis. Despite stimulated macrophage activation, osteophyte formation was fully prevented. Our in vivo study showed that intra-articular injections with TA strongly enhanced FRβ + macrophage activation. 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. To further explain the outcomes of our in vivo study, TA on macrophages was also studied in vitro. Articular cartilage was analyzed at 6 and 12 weeks with ex vivo contrast-enhanced μCT and histology. Synovial macrophage activation was measured in vivo using folate receptor β (FRβ)-targeted single-photon emission computed tomography/computed tomography. Untreated and TA-treated animals were longitudinally monitored for 12 weeks with in vivo micro–computed tomography (μCT) to measure subchondral bone changes. Osteoarthritis was induced in rat knees using papain injections and a running protocol. Furthermore, in vitro macrophage differentiation experiments were conducted to further explain working mechanisms of TA effects found in vivo. In this animal study, we investigated the in vivo effects of TA injections on macrophage activation, osteophyte development and joint degeneration. Although widely applied in clinical care, the mechanism through which TA exerts this effect remains unknown. TA injections might influence macrophage activation and subsequently reduce osteophytosis. Osteophyte formation is known to be facilitated by synovial macrophage activation. Triamcinolone acetonide (TA) is used for osteoarthritis management to reduce pain, and pre-clinical studies have shown that TA limits osteophyte formation.
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