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

• Published in: Life sciences (1973) Vol. 231; p. 116556
• Main Authors: Olímpio, Regiane Marques Castro, Moretto, Fernanda Cristina Fontes, De Sibio, Maria Teresa, de Oliveira, Miriane, Mathias, Lucas Solla, Gonçalves, Bianca Mariani, Deprá, Igor Carvalho, Tilli, Helena Paim, Rodrigues, Bruna Moretto, Saraiva, Patrícia Pinto, Maria, Durvanei Augusto, Nogueira, Célia Regina
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15-08-2019; Elsevier BV
• Subjects: Alizarin; Alkaline phosphatase; Biomedical materials; Bone mass; Bone matrix; Bone remodeling; Enzyme-linked immunosorbent assay; Estrogen; Estrogens; Gene expression; Hormones; Hyperthyroidism; Menopause; Mimicry; Osteoblast; Osteoblasts; Osteocalcin; Osteoprotegerin; Physiological effects; Physiology; RANKL and OPG; Signal transduction; Signaling; Stem cells; Thyroid hormones; TRANCE protein; Triiodothyronine; Osteoblast; Triiodothyronine; RANKL and OPG; Stem cells; Estrogen
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2019.116556

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.