[Wnt signaling and glucocorticoid-induced osteoporosis].
Wnt signaling plays an important role not only in development and morphogenesis of embryos but in pathogenesis of various disorders including cancers. Analyses of the mutations in LDL receptor-related protein 5 (LRP5), a Wnt co-receptor, revealed that the Wnt signaling pathway is important for bone formation. Glucocorticoids suppress the canonical Wnt signaling pathway by such mechanisms as the enhancement the expression of dickkopf-1 (Dkk-1) and secreted frizzled-related protein 1 (sFRP1), and activation of the glycogen synthase kinase-3beta (GSK-3beta) activity. The inhibition of the canonical Wnt signal by glucocorticoid may be involved in the pathogenesis of glucocorticoid-induced osteoporosis.
Ohnaka
Keizo
K
Kyushyu University, Graduate School of Medical Sciences, Department of Geriatric Medicine.
D000818:Animals; D015519:Bone Density / Q000235:genetics; D005938:Glucocorticoids / Q000009:adverse effects*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis / Q000235:genetics; D010024:Osteoporosis / Q000139:chemically induced*; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
D005938:Glucocorticoids; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051153:Wnt Proteins; D051176:beta Catenin; C501126:DKK1 protein, human; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C000605506:GSK3B protein, human