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

Author(s):Show less -

Castro Olimpio, Regiane Marques ^[1] ; Fontes Moretto, Fernanda Cristina ^[1] ; De Sibio, Maria Teresa ^[1] ; de Oliveira, Miriane ^[1] ; Mathias, Lucas Solla ^[1] ; Goncalves, Bianca Mariani ^[1] ; Depra, Igor Carvalho ^[1] ; Tilli, Helena Paim. ^[1] ; Rodrigues, Bruna Moretto ^[1] ; Saraiva, Patricia Pinto ^[1] ; Maria, Durvanei Augusto ^[2] ; Nogueira, Celia Regina ^[1]

Affiliation

^[1] Univ Estadual Paulista UNESP, Botucatu Med Sch, Dept Internal Med, BR-18618970 Botucatu, SP - Brazil

^[2] Butantan Inst, Biochem & Biophys Lab, 1500 Ave Vital Brazil, Sao Paulo - Brazil

• Document type: Journal article
• Source: Life Sciences; v. 231, AUG 15 2019.
• Web of Science Citations: 0

Abstract

Triiodothyronine (T-3) and estrogen (E-2) play important roles in the bone remodeling process and signaling of receptor activator of the nuclear factor-kappa beta (RANKL) and osteoprotegerin (OPG) expressed by osteoblasts. However, little is known of the molecular action of these hormones in conditions of hyperthyroidism and associated E-2 in human cells. AIMS: This study evaluated the effects of the physiological concentration of E-2 (10 nM), alone or in association with physiological (1 nM) and supraphysiological (10 nM) concentrations of T-3, 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 E-2, 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: E-2 enhanced the gene expression of OPG when associated with 1 nM and 10 nM T-3. E-2 was able to restore the bone matrix after an initial decrease using 1 nM and 10 nM T-3. The protective effect of E-2 on the RANKL and OPG signaling pathway was demonstrated. E-2 restored the bone matrix induced by experimental hyperthyroidism. SIGNIFICANCE: The data highlight the importance of E-2 to maintain OPG expression and osteoblast activity against possible loss of bone mass, especially in conditions where T-3 is in excess. (AU)

• FAPESP's process: 14/16406-9 - EVALUATION OF ACTION ESTROGEN AND THYROID HORMONE ACTION UPON NONCODING RNA EXPRESSION IN OSTEOBLASTIC CELLS DERIVED OF ADIPOSE TISSUE
• Grantee: Celia Regina Nogueira
• Support Opportunities: Regular Research Grants