TY - JOUR
T1 - Genistein Triggers Translocation of Estrogen Receptor-Alpha in Mitochondria to Induce Expressions of ATP Synthesis-Associated Genes and Improves Energy Production and Osteoblast Maturation
AU - Wu, Gong Jhe
AU - Cherng, Yih Giun
AU - Chen, Jui Tai
AU - Chang, Chuen Chau
AU - Liu, Shing Hwa
AU - Chen, Ruei Ming
N1 - Publisher Copyright:
© 2021
PY - 2021
Y1 - 2021
N2 - Our previous study showed that estrogen can induce mitochondrial adenosine triphosphate (ATP) synthesis-associated gene expressions and osteoblast maturation. Genistein, a phytoestrogenic isoflavone that is widely found in various foods and traditional herb products, is beneficial for osteogenesis by selectively triggering estrogen receptor alpha (ERα) expression. In this study, we further investigated the mechanisms of genistein-induced energy production and osteoblast activation. Exposure of rat calvarial osteoblasts and human U-2 OS cells to genistein triggered osteoblast activation without affecting cell survival. Treatment with genistein time-dependently induced ERα mRNA and protein expressions in rat calvarial osteoblasts. Analyses by confocal microscopy and immunoblotting showed that genistein stimulated translocation of ERα from the cytoplasm to mitochondria. Subsequently, expressions of mitochondrial cytochrome c oxidase (COX) I and II mRNAs and proteins in primary rat osteoblasts were induced after exposure to genistein. Knocking-down ERα concurrently inhibited genistein-induced COX I and II mRNA expressions. In addition, mitochondrial complex enzyme activities, the mitochondrial membrane potential, and cellular ATP levels in rat calvarial osteoblasts were time-dependently augmented by genistein. Suppressing ERα expression instantaneously lowered genistein-induced enhancements of mitochondrial energy production and osteoblast activation. Effects of genistein on ERα translocation, COX I and II mRNA expressions, ATP synthesis, and osteoblast activation were further confirmed in human U-2 OS cells. This study showed that genistein can stimulate energy production and consequent osteoblast activation via inducing ERα-mediated mitochondrial ATP synthesis-linked gene expressions.
AB - Our previous study showed that estrogen can induce mitochondrial adenosine triphosphate (ATP) synthesis-associated gene expressions and osteoblast maturation. Genistein, a phytoestrogenic isoflavone that is widely found in various foods and traditional herb products, is beneficial for osteogenesis by selectively triggering estrogen receptor alpha (ERα) expression. In this study, we further investigated the mechanisms of genistein-induced energy production and osteoblast activation. Exposure of rat calvarial osteoblasts and human U-2 OS cells to genistein triggered osteoblast activation without affecting cell survival. Treatment with genistein time-dependently induced ERα mRNA and protein expressions in rat calvarial osteoblasts. Analyses by confocal microscopy and immunoblotting showed that genistein stimulated translocation of ERα from the cytoplasm to mitochondria. Subsequently, expressions of mitochondrial cytochrome c oxidase (COX) I and II mRNAs and proteins in primary rat osteoblasts were induced after exposure to genistein. Knocking-down ERα concurrently inhibited genistein-induced COX I and II mRNA expressions. In addition, mitochondrial complex enzyme activities, the mitochondrial membrane potential, and cellular ATP levels in rat calvarial osteoblasts were time-dependently augmented by genistein. Suppressing ERα expression instantaneously lowered genistein-induced enhancements of mitochondrial energy production and osteoblast activation. Effects of genistein on ERα translocation, COX I and II mRNA expressions, ATP synthesis, and osteoblast activation were further confirmed in human U-2 OS cells. This study showed that genistein can stimulate energy production and consequent osteoblast activation via inducing ERα-mediated mitochondrial ATP synthesis-linked gene expressions.
KW - Energy Production
KW - Estrogen Receptor Alpha
KW - Genistein
KW - Mitochondrial Gene Expression
KW - Osteoblast Maturation
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U2 - 10.1142/S0192415X21500439
DO - 10.1142/S0192415X21500439
M3 - Article
C2 - 33853499
AN - SCOPUS:85104312019
SN - 0192-415X
VL - 49
SP - 901
EP - 923
JO - Comparative Medicine East and West
JF - Comparative Medicine East and West
IS - 4
ER -