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Lentivirus-delivered ACE siRNA rescues the impaired peak bone mass accumulation caused by prenatal dexamethasone exposure in male offspring rats

Abstract : Angiotensin I converting enzyme (ACE) is a major component of the renin-angiotensin system (RAS). Our previous study demonstrated that activated bone RAS was associated with low peak bone mass induced by prenatal dexamethasone exposure (PDE) in male offspring rats. However, we did not determine whether the inhibition of ACE expression could rescue PDE-induced low peak bone mass. In the present study, we treated pregnant Wistar rats with dexamethasone (0.2 mg/kg.d) on gestational days 9–20 and obtained eight weeks old male offspring rats. Some of the offspring rats from the PDE group were injected lentivirus delivered-ACE siRNA (LV-ACE siRNA) through the intra-bone marrow for 4 weeks. We found that the intra-bone marrow injection of LV-ACE siRNA rescued the impaired peak bone mass accumulation caused by PDE in male offspring rats. Moreover, LV-ACE siRNA ameliorated PDE-induced inhibition of osteogenesis and alleviated PDE-induced RAS activation in the bone tissues in vivo. Our in vitro findings further confirmed that LV-ACE siRNA reversed the suppressed osteogenic differentiation caused by dexamethasone, which can be attributed to alleviated RAS activation. In conclusion, LV-ACE siRNA rescued impaired peak bone mass accumulation caused by PDE through alleviation of local bone RAS activation in male offspring rats.
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https://hal.univ-lorraine.fr/hal-02969225
Contributor : Céline Huselstein Connect in order to contact the contributor
Submitted on : Friday, October 16, 2020 - 2:35:29 PM
Last modification on : Thursday, September 1, 2022 - 3:55:32 AM

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Hao Xiao, Yinxian Wen, Zhixin Wu, Haitao Chen, Jacques Magdalou, et al.. Lentivirus-delivered ACE siRNA rescues the impaired peak bone mass accumulation caused by prenatal dexamethasone exposure in male offspring rats. BONE, Elsevier, 2020, pp.115578. ⟨10.1016/j.bone.2020.115578⟩. ⟨hal-02969225⟩

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