{"id":163044,"date":"2025-01-20T14:31:17","date_gmt":"2025-01-20T13:31:17","guid":{"rendered":"https:\/\/stratec-med.com\/literatur\/disabling-of-receptor-activator-of-nuclear-factor-kappab-rank-receptor-complex-by-novel-osteoprotegerin-like-peptidomimetics-restores-bone-loss-in-vivo-2\/"},"modified":"2025-01-20T14:31:17","modified_gmt":"2025-01-20T13:31:17","slug":"disabling-of-receptor-activator-of-nuclear-factor-kappab-rank-receptor-complex-by-novel-osteoprotegerin-like-peptidomimetics-restores-bone-loss-in-vivo-2","status":"publish","type":"literatur","link":"https:\/\/stratec-med.com\/en\/literature\/disabling-of-receptor-activator-of-nuclear-factor-kappab-rank-receptor-complex-by-novel-osteoprotegerin-like-peptidomimetics-restores-bone-loss-in-vivo-2\/","title":{"rendered":"Disabling of receptor activator of nuclear factor-kappaB (RANK) receptor complex by novel osteoprotegerin-like peptidomimetics restores bone loss in vivo"},"content":{"rendered":"<p>The tumor necrosis factor family ligand, tumor necrosis factor-related activation-induced cytokine (TRANCE), and its receptors, receptor activator of nuclear factor-kappaB (RANK) and osteoprotegerin (OPG), are known to be regulators of development and activation of osteoclasts in bone remodeling. Sustained osteoclast activation that occurs through TRANCE-RANK causes osteopenic disorders such as osteoporosis and contributes to osteolytic metastases. Here, we report a rationally designed small molecule mimic of osteoprotegerin to inhibit osteoclast formation in vitro and limit bone loss in an animal model of osteoporosis. One of the mimetics, OP3-4, significantly inhibited osteoclast formation in vitro (IC(50) = 10 microm) and effectively inhibited total bone loss in ovariectomized mice at a dosage of 2 mg\/kg\/day. Unlike soluble OPG receptors, which preclude TRANCE binding to RANK, OP3-4 shows the ability to modulate RANK-TRANCE signaling pathways and alters the biological functions of the RANK-TRANCE receptor complex by facilitating a defective receptor complex. These features suggest that OPG-derived small molecules can be used as a probe to understand complex biological functions of RANK-TRANCE-OPG receptors and also can be used as a platform to develop more useful therapeutic agents for inflammation and bone disease.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The tumor necrosis factor family ligand, tumor necrosis factor-related activation-induced cytokine (TRANCE), and its receptors, receptor activator of nuclear factor-kappaB<\/p>\n","protected":false},"author":22,"parent":0,"menu_order":0,"template":"","format":"standard","meta":{"_acf_changed":false},"tags":[],"thema":[5866,5920],"produktgruppe":[5825],"literatur_kategorie":[7223],"class_list":["post-163044","literatur","type-literatur","status-publish","format-standard","hentry","thema-diagnostics-using-leonardo-pqct","thema-pre-clinical-research","produktgruppe-pqct-en","literatur_kategorie-pre-clinical-studies"],"acf":[],"_links":{"self":[{"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/literatur\/163044","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/literatur"}],"about":[{"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/types\/literatur"}],"author":[{"embeddable":true,"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/users\/22"}],"version-history":[{"count":0,"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/literatur\/163044\/revisions"}],"wp:attachment":[{"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/media?parent=163044"}],"wp:term":[{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/tags?post=163044"},{"taxonomy":"thema","embeddable":true,"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/thema?post=163044"},{"taxonomy":"produktgruppe","embeddable":true,"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/produktgruppe?post=163044"},{"taxonomy":"literatur_kategorie","embeddable":true,"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/literatur_kategorie?post=163044"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}