Bone anabolic action of PTH has been suggested to be mediated by induction of IGF-I in osteoblasts; however, little is known about the molecular mechanism by which IGF-I leads to bone formation under the PTH stimulation. This study initially confirmed in mouse osteoblast cultures that PTH treatment increased IGF-I mRNA and protein levels and alkaline phosphatase activity, which were accompanied by phosphorylations of IGF-I receptor, insulin receptor substrate (IRS)-1 and IRS-2, essential adaptor molecules for the IGF-I signaling. To learn the involvement of IRS-1 and IRS-2 in the bone anabolic action of PTH in vivo, IRS-1-\/- and IRS-2-\/- mice and their respective wild-type littermates were given daily injections of PTH (80 mug\/kg) or vehicle for 4 wk. In the wild-type mice, the PTH injection increased bone mineral densities of the femur, tibia, and vertebrae by 10-20% without altering the serum IGF-I level. These stimulations were similarly seen in IRS-2-\/- mice; however, they were markedly suppressed in IRS-1-\/- mice. Although the PTH anabolic effects were stronger on trabecular bones than on cortical bones, the stimulations on both bones were blocked in IRS-1-\/- mice but not in IRS-2-\/- mice. Histomorphometric and biochemical analyses showed an increased bone turnover by PTH, which was also blunted by the IRS-1 deficiency, though not by the IRS-2 deficiency. These results indicate that the PTH bone anabolic action is mediated by the activation of IRS-1, but not IRS-2, as a downstream signaling of IGF-I that acts locally as an autocrine\/paracrine factor.<\/p>\n","protected":false},"excerpt":{"rendered":"
Bone anabolic action of PTH has been suggested to be mediated by induction of IGF-I in osteoblasts; however, little is<\/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-163116","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\/163116","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\/163116\/revisions"}],"wp:attachment":[{"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/media?parent=163116"}],"wp:term":[{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/tags?post=163116"},{"taxonomy":"thema","embeddable":true,"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/thema?post=163116"},{"taxonomy":"produktgruppe","embeddable":true,"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/produktgruppe?post=163116"},{"taxonomy":"literatur_kategorie","embeddable":true,"href":"https:\/\/stratec-med.com\/en\/wp-json\/wp\/v2\/literatur_kategorie?post=163116"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}