INTRODUCTION: @entity2995 (TA) is used for @entity571 management to reduce @entity158 , and pre-clinical studies have shown that TA limits @entity5040 formation. @entity5040 formation is known to be facilitated by synovial macrophage activation. TA injections might influence macrophage activation and subsequently reduce @entity28489 . 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, @entity5040 development and @entity528 . Furthermore, in vitro macrophage differentiation experiments were conducted to further explain working mechanisms of TA effects found in vivo. METHODS: @entity571 was induced in @entity35 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 @entity1501 receptor b (FRb)-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 @entity40679 and FRb expression as well as for messenger RNA (mRNA) expression of @entity13358 . RESULTS: Our in vivo study showed that intra-articular injections with TA strongly enhanced FRb(+) macrophage activation. Despite stimulated macrophage activation, @entity5040 formation was fully prevented. There was no beneficial effect of TA against cartilage degradation or subchondral @entity79 . In vitro macrophage cultures showed that TA strongly induced monocyte differentiation towards @entity40679 (+) and FRb(+) macrophages. Furthermore, TA-stimulated M2 macrophages showed enhanced @entity13358 expression at the mRNA level. CONCLUSIONS: TA injections potently induce a @entity40679 (+)- and FRb(+)-activated macrophage with anti-inflammatory characteristics such as reduced @entity13358 production in vitro and lack of @entity28489 in vivo.

@entity2995 activates an anti-inflammatory and XXXX receptor-positive macrophage that prevents @entity28489 in vivo.

@entity1501 :: ('MESH:D005492', 'Chemical') :: ['folate'] @entity2995 :: ('MESH:D014222', 'Chemical') :: ['Triamcinolone acetonide'] @entity571 :: ('MESH:D010003', 'Disease') :: ['Osteoarthritis', 'osteoarthritis'] @entity40679 :: ('312701(Tax:10116)', 'Gene') :: ['CD163'] @entity13358 :: ('25325(Tax:10116)', 'Gene') :: ['interleukin (IL)-10', 'IL-10'] @entity28489 :: ('MESH:D013128', 'Disease') :: ['osteophytosis'] @entity5040 :: ('MESH:D054850', 'Disease') :: ['osteophyte', 'Osteophyte'] @entity79 :: ('MESH:D001847', 'Disease') :: ['bone sclerosis'] @entity158 :: ('MESH:D010146', 'Disease') :: ['pain'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity528 :: ('MESH:D009410', 'Disease') :: ['joint degeneration']
@entity1501 :: (MESH:D005492,Chemical) :: ['folate']
