Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, No.1838 North of Guangzhou Avenue, Guangzhou, 510515, Guangdong Province, China.
Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Stem Cell Res Ther. 2020 Jul 6;11(1):270. doi: 10.1186/s13287-020-01790-9.
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 CD45CD29CD105Sca-1 bone marrow mesenchymal stem cells (BMSCs) and CD45Nestin 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.
产前地塞米松暴露（PDE）会导致胎儿出生体重降低和骨骼发育迟缓，这与成年后代的峰值骨量降低有关。在此，我们评估了 PDE 是否以及如何影响幼鼠后代出生后的长骨生长。
妊娠小鼠从妊娠第 12-14 天每天早上经皮下注射地塞米松（1.2mg/kg/天）。2、4、6 和 12 周龄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 导致雌性幼鼠长骨骨重建受损和骨量减少。在出生后骨生长过程中，PDE 后幼鼠长骨干骺端发现 CD45CD29CD105Sca-1 骨髓间充质干细胞（BMSCs）和 CD45Nestin 细胞明显减少、H 型血管丢失以及细胞衰老增加。我们进一步表明，在妊娠第 12-14 天用达沙替尼（5mg/kg/天）和槲皮素（50mg/kg/天）消除过多的衰老细胞可挽救 PDE 对雌性幼鼠出生后长骨生长的毒性作用。
细胞衰老介导了 PDE 对幼鼠出生后长骨生长的毒性作用，抑制细胞衰老可能被提出用于治疗 PDE 引起的骨生长迟缓。
