{"id":858,"date":"2025-06-16T23:31:44","date_gmt":"2025-06-16T23:31:44","guid":{"rendered":"http:\/\/wmtc2006.com\/?p=858"},"modified":"2025-06-16T23:31:44","modified_gmt":"2025-06-16T23:31:44","slug":"this-is-in-accordance-with-our-previous-results-6","status":"publish","type":"post","link":"https:\/\/wmtc2006.com\/?p=858","title":{"rendered":"\ufeffThis is in accordance with our previous results [6]"},"content":{"rendered":"

\ufeffThis is in accordance with our previous results [6]. The histological destruction found in paw sections was not as severe as in some previous studies [10,12], and this was due most probably to the short experiment protocol (2 weeks of disease). Serum levels of COMP reflect the degree of cartilage destruction during arthritic disease [2729]. during the induction phase of CIA failed to affect arthritis. Raloxifene did not hamper disease activity in CAIA, whereas oestradiol delayed the onset and ameliorated the severity. Both raloxifene and oestradiol preserved BMD in CAIA. CII-immunization increased the oestradiol-induced ERE activation in spleen, and raloxifene activated the ERE at about 25% the intensity of oestradiol. Further experiments are needed to elucidate the exact mechanisms behind this finding. Keywords:BMD, CAIA, CIA, oestradiol, luciferase-ERE, ovariectomy, raloxifene == Introduction == Rheumatoid arthritis (RA) is a progressive systemic autoimmune disease, causing great morbidity. Both focal joint erosions and generalized osteoporosis result in a disabling disease. The prevalence is 051% worldwide [1], with a female to male ratio of 3:1, and the prevalence of concurrent osteoporosis is 50% [2,3]. The female sex steroid oestradiol has been shown to be beneficial in postmenopausal osteoporosis, and also to influence the incidence and progression of RA. We have previously reported decreased joint destruction and disease progression in postmenopausal RA patients treated with oestrogen-containing hormone replacement therapy (HRT) [4]. Unfortunately, HRT has been associated with severe side effects [5], and is no longer recommended for long-term therapy. Therefore, there is a need to find alternative oestrogen-like substances with the beneficial properties, and lacking the side effects. We and others have shown previously that administration of both oestradiol and raloxifene, a selective oestrogen receptor modulator (SERM) approved for the treatment of postmenopausal osteoporosis, can ameliorate collagen-induced arthritis (CIA), a murine model of human RA [6,7]. Even when treatment was initiated in mice with severe, established disease, these effects were substantial [7]. Also, when oestradiol was administered (at doses equivalent to estrus, resulting in serum levels of 400 pg\/ml, or 50% of Cyclo(RGDyK) pregnancy levels, with serum levels of 4000 pg\/ml) from 7 days Cyclo(RGDyK) prior to immunization until termination, three different mouse models failed to develop arthritis [8]. In addition to the anti-arthritic properties, treatment with raloxifene also prevented arthritis-induced osteoporosis development [6,7]. CIA and the loss of endogenous oestrogen after ovariectomy (OVX) have been shown to contribute to osteoporosis development in an additive way [9]. In the present study we wanted to investigate whether raloxifene would display anti-arthritic effects with treatment only during the induction phase of CIA, or during the effector phase of the disease. For treatment during the induction phase we used the CIA model, and treated the mice from 2 days pre- to 10 days postimmunization. Treatment during the effector phase was evaluated using the collagenantibody-induced arthritis (CAIA) model [10]. In CAIA, the introduction of preformed antibodies induces arthritis. Antibodies to collagen II (CII) have been shown previously to be involved in both human and experimental RA [11], and oestradiol has been shown to hamper the disease in CAIA [12]. Oestrogens activate target genes via various signalling pathways, including the classical pathway, in which oestrogen receptors (ER) and bind to oestrogen response elements (ERE) on DNA, and thereby promote gene transcription. We therefore wanted to investigate whether the ERE is activated by CII immunization, and whether raloxifene can Cyclo(RGDyK) activate this pathway. To this end, we used a transgenic ERE-luciferase (Luc) reporter mouse model [13]. One Rabbit polyclonal to ZC4H2<\/a> recent 10-week Phase II clinical Cyclo(RGDyK)<\/a> trial Cyclo(RGDyK) investigated an agonist of ER (Org 37663) in postmenopausal RA, and found no clinical benefit despite induction of oestrogenic responses in several organ systems [14]. In another recent 12-week Phase II trial an agonist of ER (ERB-041) was investigated, and similar results were found [15]. One explanation may be that the duration of the trials was not long enough to induce clinical benefit, as a previous trial with HRT showed benefit only after 2 years. As animal studies with both compounds had shown anti-arthritic properties, it is important to investigate further the mechanisms for these effects, and to evaluate whether there is a difference between different species [16,17]. Indeed, we have shown previously that stimulation of ER ameliorated CIA in.<\/p>\n","protected":false},"excerpt":{"rendered":"

\ufeffThis is in accordance with our previous results [6]. 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