Glucocorticoid therapy suppresses Wnt signaling by reducing the ratio of serum Wnt3a to Wnt inhibitors, sFRP-1 and Wif-1.
Clin Rheumatol
; 40(7): 2947-2954, 2021 Jul.
Article
em En
| MEDLINE
| ID: mdl-33420868
ABSTRACT
OBJECTIVE:
Our previous study suggested that suppression of Wnt/ß-catenin signaling by increasing serum Wnt co-receptor inhibitors, sclerostin and Dickkopf-1, impairs bone formation in the first week after starting glucocorticoid therapy. The objective of this study was to investigate the involvement of the Wnt/ß-catenin signaling pathway and its clinical significance in the subsequent suppression of bone formation.METHODS:
A total of 53 patients with systemic autoimmune diseases who received initial glucocorticoid therapy with prednisolone (30-60 mg daily) were prospectively enrolled. We measured serum levels of Wnt3a and Wnt inhibitors, secreted Frizzled-related protein 1 (sFRP-1) and Wnt inhibitory factor 1 (Wif-1), before starting glucocorticoid therapy and every week for 4 weeks after its initiation.RESULTS:
Serum levels of sFRP-1 and Wif-1 slightly decreased compared with before glucocorticoid therapy from the second week. The serum Wnt3a level decreased from the first week. The ratios of Wnt3a to sFRP-1 and that of Wnt3a to Wif-1 both decreased from the first week onward.CONCLUSION:
The reduction of the ratio of Wnt3a to Wnt inhibitors, sFRP-1 and Wif-1, suppresses Wnt signaling, which may result in impaired bone formation. Taken together with our previous studies, glucocorticoids may suppress Wnt signaling by inhibiting co-receptors of the Wnt/ß-catenin signaling pathway in the early phase of glucocorticoid therapy and inhibiting its ligand in the subsequent weeks, which together impair bone formation. Key Points ⢠The decrease in Wnt pathway-related molecules by glucocorticoids impairs bone formation. ⢠Glucocorticoids inhibit co-receptors of Wnt signaling in the early phase of therapy. ⢠Glucocorticoids inhibit ligands of Wnt signaling in the subsequent phase of therapy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
/
Via de Sinalização Wnt
/
Glucocorticoides
Limite:
Humans
Idioma:
En
Revista:
Clin Rheumatol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Japão