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GR/HDAC2/TGFβR1 pathway contributes to prenatal caffeine induced-osteoarthritis susceptibility in male adult offspring rats

Abstract : Prenatal caffeine exposure (PCE) induces developmental toxicity of multi-organ and susceptibility to multi-disease in offspring. However, the effects of PCE on osteoarthritis susceptibility in adult offspring and its intrauterine programming mechanism remain to be further investigated. Here, we found that PCE induced susceptibility to osteoarthritis in male adult offspring rats, which was related to the inhibited function of cartilage matrix synthesis from fetuses to adults. Meanwhile, PCE consistently downregulated the H3K9ac and expression levels of transforming growth factor β receptor 1 (TGFβR1), and then blocked TGFβ signaling pathway, which contributed to the suppressed cartilage matrix synthesis. Moreover, the high level of corticosterone caused by PCE reduced the H3K9ac level on TGFβR1 promoter region through acting on glucocorticoids receptor (GR) and recruiting histone deacetylase 2 (HDAC2) into the nucleus of fetal chondrocytes. Taken together, PCE induced osteoarthritis susceptibility in male adult offspring rats, which was attributed to the low-functional programming of TGFβR1 induced by corticosterone via GR/HDAC2 signaling.
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https://hal.univ-lorraine.fr/hal-02969253
Contributor : Céline Huselstein Connect in order to contact the contributor
Submitted on : Friday, October 16, 2020 - 2:49:10 PM
Last modification on : Thursday, September 1, 2022 - 11:05:37 AM

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Jing Li, Hao Xiao, Hanwen Luo, Yang Tan, Qubo Ni, et al.. GR/HDAC2/TGFβR1 pathway contributes to prenatal caffeine induced-osteoarthritis susceptibility in male adult offspring rats. Food and Chemical Toxicology, 2020, 140, pp.111279. ⟨10.1016/j.fct.2020.111279⟩. ⟨hal-02969253⟩

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