Infraphysiological 17 beta-estradiol (E2) concentration compromises osteoblast differentiation through Src stimulation of cell proliferation and ECM remodeling stimulus

Autor(es)

Barneze Costa, Sarah Maria ^[1] ; Feltran, Georgia Silva ^[2] ; Namba, Vickeline ^[1] ; Silva, Tabata Marilda ^[1] ; Hallur, Raghavendra Lakshmana Shetty ^{[1, 3]} ; Saraiva, Patricia Pinto ^[1] ; Zambuzzi, Willian Fernando ^[2] ; Nogueira, Celia Regina ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Sch Med Botucatu FMB, Expt Res Unit, BR-18618970 Botucatu, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Biosci Inst, Dept Chem & Biochem, BR-18618970 Botucatu, SP - Brazil

^[3] Sao Paulo State Univ UNESP, Sch Med Botucatu FMB, Dept Gynecol & Obstet, BR-18618970 Botucatu, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Cellular Endocrinology; v. 518, DEC 1 2020.
• Citações Web of Science: 0

Resumo

It has been shown that 17 beta-estradiol (E2) helps to prevent bone loss. This study was undertaken to verify whether E2 action in human osteoblasts involves changes in the transcriptional profile of the TNF-alpha, IFN-gamma, NF-kappa B, TRAIL, TGF-beta, MMP2, MMP9, RECK, TIMP1, TIMP2, CDK2, CDK4, SRC, RUNX2, and SHH genes. Infraphysiological doses of E2 elevated mRNAs in all genes except for INF-gamma, TRAIL, and TGF-beta. Importantly, a significant increase in the CDKs -2 and -4 genes was found, which strongly suggests cell cycle progression, with a potential dependency of Src involvement, as well as a suppression of the osteoblast differentiation machinery, with ECM remodeling being involved. These data suggest that E2 plays an important role in bone formation and remodeling, and Src seems to play a pivotal role in driving cell proliferation and ECM remodeling. Taken together, these findings contribute to an understanding of the effects of infraphysiological E2 on modulating bone homeostasis, favoring bone resorption, and leading to osteoporosis. (AU)

• Processo FAPESP: 14/15529-0 - Efeito do estrógeno e do hormônio tireoidiano na expressão gênica e protéica de RANKL e TNF-± em células osteoblásticas derivadas do tecido adiposo
• Beneficiário: Sarah Maria Barneze Costa
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 14/22689-3 - Sinalização parácrina mediada por microvesículas e proteínas entre células ósseas e endoteliais durante o desenvolvimento e regeneração do tecido ósseo
• Beneficiário: Willian Fernando Zambuzzi
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 14/16406-9 - AVALIAÇÃO DA AÇÃO DO ESTRÓGENO E DO HORMÔNIO TIREOIDIANO NA EXPRESSÃO DOS RNAs NÃO CODIFICANTES EM CÉLULAS OSTEOBLÁSTICAS DERIVADAS DO TECIDO ADIPOSO
• Beneficiário: Celia Regina Nogueira
• Modalidade de apoio: Auxílio à Pesquisa - Regular