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/婴儿生长所需钙的重要来源。这导致了母体骨量的大量流失。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载荷。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。在女性生殖过程中，骨骼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）项目将增加我们对骨骼结构、机械特性的变化以及骨细胞对由于生育而发生的机械力的反应的科学知识。通过教育计划，本项目将激发高中学生对骨生物学和力学的兴趣，促进本科学生在肌肉骨骼工程和科学方面的跨学科学习和研究，并加强与公众就骨生物学、结构和力学的教育背景进行交流。该项目的第一个目标是量化生理承重的影响，并确定骨骼对妊娠和哺乳的机械敏感性对骨骼反应的影响。小梁骨和皮质骨结构、力学和重塑活动将在日常活动中承受不同负荷的多个骨骼部位之间进行比较。将比较未交配大鼠和处于不同生殖阶段的大鼠在胫骨轴向载荷下的低至高峰应变对骨形成的影响程度。该项目的第二个目标是确定怀孕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，以评估腔隙和管状结构、腔隙周围骨组织材料特性的变化，以及骨细胞所经历的负载诱导的流体流动刺激及其在女性生殖不同阶段的反应过程。本研究将发现和了解骨细胞在调节其微力学环境和力学敏感性以维持母体骨骼完整性方面的新功能，并为孕期和哺乳期骨质疏松症的预防和管理提供见解。

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.