The role of Wnt signaling and sclerostin in the pathogenesis of glucocorticoid-induced osteoporosis.
Bone formation is suppressed in glucocorticoid-induced osteoporosis. One of the mechanisms by which glucocorticoids depress bone formation is through their effects on the Wnt/β-catenin signaling pathway, a critical regulator of osteoblastogenesis. Thus, Wnt signaling induces the differentiation of osteoblast precursors toward mature osteoblasts and prevents osteoblast and osteocyte apoptosis. Glucocorticoids increase the expression of Wnt signaling antagonists (sclerostin and Dkk-1) in experimental studies in rodents and cell cultures. However, the scarce data of their effects in humans are somewhat contradictory, probably due to the dose and duration of treatment as well as the characteristics of the patients. A progressive decrease in Dkk-1 serum levels and an increase in circulating sclerostin levels at long-term follow-up have recently been reported in patients treated with high doses of glucocorticoids. This review describes the most recent data on the effects of glucocorticoids on the Wnt signaling pathway, especially on their antagonists, sclerostin and Dkk-1.
Department of Rheumatology, Hospital Clínic, C/Villarroel 170, Barcelona, 08036, Spain, nguanabens@ub.edu.
Núria
N
Guañabens
Laia
L
Gifre
Pilar
P
Peris
D048868:Adaptor Proteins, Signal Transducing; D015519:Bone Density / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D005819:Genetic Markers / Q000502:physiology*; D005938:Glucocorticoids / Q000009:adverse effects*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D010024:Osteoporosis / Q000139:chemically induced* / Q000503:physiopathology; D058866:Osteoporotic Fractures / Q000503:physiopathology; D015398:Signal Transduction; D060449:Wnt Signaling Pathway / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D005938:Glucocorticoids; D036341:Intercellular Signaling Peptides and Proteins; C422903:SOST protein, human