CAREER: Temporal Changes In Rat Maternal Bone During Lactation And After Weaning

在怀孕和哺乳期间，母体骨骼是胎儿/婴儿生长的重要钙源。这导致母体骨量的大量损失。然而，与此同时，骨骼也必须继续执行其机械功能，承受日常活动中施加的负荷。这种平衡是通过怀孕和哺乳期间的适应以及断奶后骨量的部分恢复来实现的，这使得母体骨骼的机械强度得以保留。骨骼在女性生殖过程中平衡这些代谢和机械功能的惊人能力背后的机制尚不清楚。通过阐明潜在的机制，这个教师早期职业发展（CAREER）计划项目将增加我们对骨结构，机械性能和骨细胞对分娩引起的机械力的反应变化的科学知识。通过教育计划，该项目将激发高中生对骨生物学和力学的兴趣，促进本科生在肌肉骨骼工程和科学方面的跨学科学习和研究，并加强与公众在骨生物学教育背景上的沟通，该项目的第一个目标是量化生理负荷的影响，并确定骨的力学效应。骨骼对妊娠和哺乳的敏感性。将在日常活动期间承受不同负荷量的多个骨骼部位之间比较小梁和皮质骨结构、力学和重塑活动。将比较未交配大鼠和不同生殖阶段大鼠对通过轴向胫骨载荷施加的一系列低至高峰应变的骨形成程度。该项目的第二个目标是确定妊娠和哺乳调节骨细胞微机械环境和机械敏感性的机制。这将通过整合先进的成像、力学测试和模拟技术来实现，以评估骨陷窝和骨小管结构、骨陷窝周围骨组织材料特性以及骨细胞及其过程在女性生殖的不同阶段所经历的负荷诱导的流体流动刺激的变化。这项研究将发现和了解骨细胞在调节其微机械环境和机械敏感性以维持母体骨骼完整性方面的新功能，并为预防和管理妊娠和哺乳期间的骨质疏松症提供见解。

During pregnancy and breastfeeding, the maternal skeleton serves as an important source of calcium for fetal/infant growth. This results in a substantial loss of maternal bone mass. However, at the same time, the skeleton must also continue to perform its mechanical function, bearing the loads applied during everyday activities. This balance is achieved through adaptations during pregnancy and lactation and partial recovery of bone mass after weaning, which allow the mechanical strength of the maternal skeleton to be preserved. The mechanisms behind the skeleton's amazing ability to balance these metabolic and mechanical functions during female reproduction are not clear. By elucidating the underlying mechanisms, this Faculty Early Career Development (CAREER) Program project will increase our scientific knowledge on the changes in bone structure, mechanical properties, and bone cells' responses to mechanical forces that occur as a result of childbearing. Through the education program, this project will inspire interest in bone biology and mechanics among high school students, foster interdisciplinary learning and research in musculoskeletal engineering and science in undergraduate students, and enhance communication with the general public on the educational context of bone biology, structure and mechanics.The first objective of this project is to quantify the effects of physiological load-bearing and determine the effects of bone's mechano-sensitivity on skeletal responses to pregnancy and lactation. Trabecular and cortical bone structure, mechanics, and remodeling activities will be compared among multiple skeletal sites that undergo various amounts of load-bearing during daily activities. The extent of bone formation in response to a range of low to high peak strains applied through axial tibial loading in virgin rats and rats at different reproductive stages will be compared. The second objective of the project is to define mechanisms by which pregnancy and lactation modulate the osteocyte micro-mechanical environment and mechano-sensitivity. This will be achieved by integrating advanced imaging, mechanical testing, and simulation techniques for assessment of changes in lacunar and canalicular structure, peri-lacunar bone tissue material properties, and load-induced fluid flow stimulation experienced by osteocytes and their processes in response to different stages of female reproduction. The proposed study will discover and understand novel functions of the osteocyte in modulating its micro-mechanical environment and mechano-sensitivity to maintain the integrity of the maternal skeleton, and provide insight into prevention and management of osteoporosis during pregnancy and lactation.