Prenatal dexamethasone exposure (PDE) induces low birth weight and retardation of fetal bone development which are associated with lower peak bone mass in adult offspring. Here we evaluated whether and how PDE affects postnatal long bone growth in mouse offspring. Pregnant mice were injected subcutaneously with dexamethasone (1.2 mg/kg/day) every morning from gestational days (GD) 12–14. Femurs and tibias of 2-, 4-, 6-, and 12-week-old female offspring were harvested for histological, immunofluorescence, flow cytometric analysis, or microcomputed tomography (μCT) measurement. PDE leads to impaired bone remodeling as well as decreased bone mass in the long bone of female mouse offspring. During postnatal bone growth, significant decrease of CD45−CD29+CD105+Sca-1+ bone marrow mesenchymal stem cells (BMSCs) and CD45−Nestin+ cells, loss of type H vessels, and increment of cellular senescence were found in metaphysis of long bone in mouse offspring after PDE. We further show that eliminating the excessive senescent cells with dasatinib (5 mg/kg/day) and quercetin (50 mg/kg/day) during GD 12–14 rescues the above toxic effect of PDE on the postnatal long bone growth in female mouse offspring. Cellular senescence mediates the toxic effect of PDE on postnatal long bone growth in mouse offspring, and inhibition of cellular senescence may be proposed for treating the retardation of bone growth caused by PDE.

中文翻译：

---

细胞衰老介导了产前地塞米松暴露对小鼠后代产后长骨生长的有害影响。

产前地塞米松暴露（PDE）会导致出生体重低和胎儿骨骼发育迟缓，这与成年后代的较低峰值骨量有关。在这里，我们评估了PDE是否以及如何影响小鼠后代的产后长骨生长。从妊娠天（GD）12-14开始，每天早上对妊娠小鼠皮下注射地塞米松（1.2 mg / kg /天）。收集2、4、6、12周大的雌性后代的股骨和胫骨，用于组织学，免疫荧光，流式细胞术分析或微计算机断层扫描（μCT）测量。PDE导致雌性小鼠后代的骨骼重塑受损以及长骨的骨量减少。在出生后骨骼生长期间，CD45-CD29 + CD105 + Sca-1 +骨髓间充质干细胞（BMSC）和CD45-Nestin +细胞显着减少，PDE后小鼠后代的长骨干meta端上发现了H型血管的缺失和细胞衰老的增加。我们进一步表明，在GD 12-14期间用达沙替尼（5 mg / kg /天）和槲皮素（50 mg / kg /天）消除过多的衰老细胞可以挽救PDE对雌性小鼠产后长骨生长的上述毒性作用后代。细胞衰老介导了PDE对小鼠后代产后长骨生长的毒性作用，因此可以提出抑制细胞衰老来治疗PDE引起的骨生长迟缓。我们进一步表明，在GD 12-14期间用达沙替尼（5 mg / kg /天）和槲皮素（50 mg / kg /天）消除过多的衰老细胞可以挽救PDE对雌性小鼠产后长骨生长的上述毒性作用后代。细胞衰老介导了PDE对小鼠后代产后长骨生长的毒性作用，因此可以提出抑制细胞衰老来治疗PDE引起的骨生长迟缓。我们进一步表明，在GD 12-14期间用达沙替尼（5 mg / kg /天）和槲皮素（50 mg / kg /天）消除过多的衰老细胞可以挽救PDE对雌性小鼠产后长骨生长的上述毒性作用后代。细胞衰老介导了PDE对小鼠后代产后长骨生长的毒性作用，因此可以提出抑制细胞衰老来治疗PDE引起的骨生长迟缓。