Abstract
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.
Highlights
Maintenance of bone mass and strength in the mammalian skeleton is orchestrated by the coordinated actions of osteoclasts responsible for the resorption of old or damaged bone and osteoblasts responsible for the deposition of new bone
We examined the effects of a maternal stressor on the maintenance of bone structure in offspring
Despite early increases in bone volume, the offspring of dams fed a high-fat diet exhibited significant bone loss as they approached adulthood. We demonstrate that this effect is primarily due to an increased abundance of osteoclastic cells and an increased sensitivity of osteoclast precursors to RANKL
Summary
Maintenance of bone mass and strength in the mammalian skeleton is orchestrated by the coordinated actions of osteoclasts responsible for the resorption of old or damaged bone and osteoblasts responsible for the deposition of new bone. With increasing age or the onset of menopause, bone resorption outpaces formation and leads to an increased risk for fragility fractures. The balances of these activities are known to be regulated by a myriad of local growth factors, hormones, and biophysical signals [1]. Genome wide association studies have identified genetic determinants for both peak bone mass and the propensity for the development of osteoporosis/osteopenia [2, 3]. We examined the effects of a maternal stressor on the maintenance of bone structure in offspring. The intrauterine environment is designed to support fetal development, Maternal High‐Fat Diet Induces Long‐Lasting Defects in Bone Structure in Rat Offspring Through
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