Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 209, Baltimore, MD, 21205, USA.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 618, Baltimore, MD, 21205, USA.
Calcif Tissue Int. 2021 May;108(5):680-692. doi: 10.1007/s00223-020-00801-4. Epub 2021 Jan 2.
Maternal stressors during the prenatal and perinatal periods are associated with increased susceptibility for and severity of chronic disease phenotypes in adult offspring. In this study, we used a rat model of maternal high-fat diet (HFD) exposure during pregnancy and lactation to investigate the impact on skeletal homeostasis in offspring. In the distal femur, young male and female offspring (up to 3 weeks of age) from dams fed a HFD exhibited marked increases in trabecular bone volume relative to offspring from dams fed a chow diet, but this was followed by sustained bone loss. By 15 weeks of age, male offspring of HFD fed dams exhibited a 33% reduction in trabecular bone volume fraction that histomorphometric analyses revealed was due to a nearly threefold increase in the abundance of bone-resorbing osteoclasts, while there were no differences between female control and HFD offspring by 15 weeks of age. The osteoblastic differentiation of male offspring-derived bone marrow stromal cells was not affected by maternal diet. However, osteoclastic precursors isolated from the male offspring of HFD fed dams exhibited enhanced differentiation in vitro, forming larger osteoclasts with higher expression of the fusion marker DC-STAMP. This effect appears to be mediated by a cell autonomous increase in the sensitivity of precursors to RANKL. Taken together, these results suggest that maternal stressors like HFD exposure have persistent consequences for the skeletal health of offspring that may ultimately lead to a predisposition for osteopenia/osteoporosis.
母体在产前和围产期的应激源与成年后代慢性疾病表型的易感性和严重程度增加有关。在这项研究中，我们使用了一种母体高脂肪饮食（HFD）暴露于怀孕和哺乳期的大鼠模型，来研究其对后代骨骼平衡的影响。在远端股骨中，来自 HFD 喂养母鼠的雄性和雌性幼崽（最多 3 周龄）相对于来自喂食标准饮食母鼠的幼崽，表现出明显增加的小梁骨体积，但随后持续发生骨丢失。到 15 周龄时，HFD 喂养母鼠的雄性后代的小梁骨体积分数减少了 33%，组织形态计量学分析显示这是由于破骨细胞的丰度增加了近三倍，而到 15 周龄时，雌性对照和 HFD 后代之间没有差异。雄性后代来源的骨髓基质细胞的成骨分化不受母体饮食的影响。然而，从 HFD 喂养母鼠的雄性后代中分离出的破骨细胞前体在体外表现出增强的分化，形成更大的破骨细胞，融合标记物 DC-STAMP 的表达更高。这种效应似乎是由前体对 RANKL 敏感性的自主增加介导的。总之，这些结果表明，像 HFD 暴露这样的母体应激源对后代的骨骼健康有持久的影响，最终可能导致骨质疏松症/骨质疏松症的易感性增加。
