The importance of estrogen for bone protection in experimental hyperthyroidism in human osteoblasts.

Abstract:

:Triiodothyronine (T3) and estrogen (E2) play important roles in the bone remodeling process and signaling of receptor activator of the nuclear factor-kappa β (RANKL) and osteoprotegerin (OPG) expressed by osteoblasts. However, little is known of the molecular action of these hormones in conditions of hyperthyroidism and associated E2 in human cells. AIMS:This study evaluated the effects of the physiological concentration of E2 (10 nM), alone or in association with physiological (1 nM) and supraphysiological (10 nM) concentrations of T3, on RANKL and OPG gene expression in human osteoblasts. MAIN METHODS:Alkaline phosphatase and osteocalcin assays were performed to verify the presence of mature osteoblasts. After mimicking the experimental hyperthyroidism in osteoblasts untreated or treated with E2, RANKL and OPG gene expression was analyzed by real-time PCR and protein expression by western Blot and ELISA. Alizarin Red staining analyzed the amount of bone matrix after hormonal treatments. KEY FINDINGS:E2 enhanced the gene expression of OPG when associated with 1 nM and 10 nM T3. E2 was able to restore the bone matrix after an initial decrease using 1 nM and 10 nM T3. The protective effect of E2 on the RANKL and OPG signaling pathway was demonstrated. E2 restored the bone matrix induced by experimental hyperthyroidism. SIGNIFICANCE:The data highlight the importance of E2 to maintain OPG expression and osteoblast activity against possible loss of bone mass, especially in conditions where T3 is in excess.

journal_name

Life Sci

journal_title

Life sciences

authors

Olímpio RMC,Moretto FCF,De Sibio MT,de Oliveira M,Mathias LS,Gonçalves BM,Deprá IC,Tilli HP,Rodrigues BM,Saraiva PP,Maria DA,Nogueira CR

doi

10.1016/j.lfs.2019.116556

subject

Has Abstract

pub_date

2019-08-15 00:00:00

pages

116556

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(19)30482-5

journal_volume

231

pub_type

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