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ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Research » Publications at this Location » Publication #356300
Title: Maternal obesity-mediated epigenetic regulation of osteoblast differentiation through SATB2

Author
item CHEN, JIN-RAN - Arkansas Children'S Nutrition Research Center (ACNC)
item ZHAO, HAIJUN - University Arkansas For Medical Sciences (UAMS)
item LAZARENKO, OXANA - University Arkansas For Medical Sciences (UAMS)
item SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 6/28/2018
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Nutritional status during intrauterine and/or early postnatal life has substantial influences on adult offspring health, mostly linked with permanent metabolic changes. However, evidence on the impact of high fat diet (HFD)-induced maternal obesity on regulation of fetal bone development is sparse. Thus, we investigated the effects of maternal obesity in rodents on both fetal skeletal development and epigenetic regulation of osteoblast differentiation in offspring. First, female Sprague-Dawley rats were fed either a low-fat AIN-93G control diet or a high fat diet (HFD) (45% fat calories) for 10 wks starting at 6 wks of age. After 10 wks of these diets, lean (from control diet) and obese (from HFD) female rats were time-impregnated (n=6 per group) by control diet male rats. At gestational day 18.5 (E18.5), all fetuses were taken and embryonic osteogenic calvarial cells (EOCCs) were isolated. We found epigenetic regulation of polycomb-regulated gene Ezh2 (Enhancer of zeste homolog 2) in embryonic rat from HFD obese dams. Increased enrichment of repressive histone mark H3K27me3 on the gene body of SATB2 (ChIP Seq analysis) was associated with aberrant differentiation of EOCCs to mature osteoblasts. Knocking down Ezh2 in EOCCs and ST2 cells increased SATB2 expression, on the other hand, Ezh2 overexpression in EOCCs and ST2 cells decreased SATB2 expression. These data were consistent with ChIP experimental results showed strong association between H3K27me3, Ezh2 and SATB2. Second, we generated pre-osteoblastic cell specific Ezh2 conditional knockout mouse model by breeding Ezh2 flox/flox and Osterix-Cre+ mice. In 6-week-old mice, we found significantly increased SATB2 mRNA and protein expression in bone from Ezh2flox/flox Osterix-Cre+ conditional knockout mice compared with those from Ezh2flox/+Cre+, Cre+, Ezh2flox/flox Cre-, Ezh2flox/+Cre- and wild type mice. These findings indicate maternal HFD-induced obesity-associated decreasing of fetal pre-osteoblastic cell differentiation is under epigenetic control through SATB2 expression.