雌性骨骼经历了显着的材料和超微结构变化,以满足繁殖和哺乳期间的高钙需求。通过腔腔周/泪小管重塑(PLR),在哺乳期间,骨细胞会主动吸收周围的基质并扩大其腔隙和小管,断奶后迅速逆转。这些变化如何改变骨细胞的物理化学环境,骨骼中最丰富和最主要的机械传感细胞,不是很了解。在这项研究中,我们开发了一种多尺度多孔弹性建模技术来研究泌乳引起的应力变化,流体加压,流体流动,和溶质在多个长度尺度上的运输(整个骨骼,多孔中轴皮质,腔隙-泪小管孔系统(LCS),和骨细胞周围的细胞周围基质(PCM))在0.5、2或4Hz的3N峰值载荷(〜320με)下受到轴向压缩的鼠胫骨。根据先前报道的泌乳和未产小鼠的骨骼解剖学测量,我们的模型证明了加载频率,LCS孔隙度,和PCM密度是负责骨细胞机械传感的流体和溶质流量的主要决定因素,细胞-细胞信号,和新陈代谢。当加载频率为0.5Hz时,泌乳诱导的LCS扩张和潜在的PCM减少促进了通过初级纤毛的溶质运输和骨细胞机械传感,但是通过细胞膜上的流体剪切和/或阻力抑制了机械传感。有趣的是,发现2或4Hz的负荷可以克服0.5Hz时观察到的机械传感缺陷,并且这些反作用在4Hz时和泌乳骨中稀疏的PCM变得更加明显。协同,较高的加载频率(2,4Hz)和稀疏的PCM增强了骨细胞的营养物质和信号分子的流动介导的机械传感和扩散/对流。总之,泌乳诱导的结构变化以有利于新陈代谢的方式改变骨细胞的局部环境,机械传感,和产妇骨骼的断奶后恢复。因此,在生殖和哺乳期间,骨细胞在平衡女性骨骼的代谢和机械功能中起作用。
The female skeleton undergoes significant material and ultrastructural changes to meet high calcium demands during reproduction and lactation. Through the peri-lacunar/canalicular remodeling (PLR), osteocytes actively resorb surrounding matrix and enlarge their lacunae and canaliculi during lactation, which are quickly reversed after weaning. How these changes alter the physicochemical environment of osteocytes, the most abundant and primary
mechanosensing cells in bone, are not well understood. In this
study, we developed a multiscale poroelastic modeling technique to investigate lactation-induced changes in stress, fluid pressurization, fluid flow, and solute transport across multiple length scales (whole bone, porous midshaft cortex, lacunar-canalicular pore system (LCS), and pericellular matrix (PCM) around osteocytes) in murine tibiae subjected to axial compression at 3 N peak load (~320 με) at 0.5, 2, or 4 Hz. Based on previously reported skeletal anatomical measurements from lactating and nulliparous mice, our models demonstrated that loading frequency, LCS porosity, and PCM density were major determinants of fluid and solute flows responsible for osteocyte mechanosensing, cell-cell signaling, and metabolism. When loaded at 0.5 Hz, lactation-induced LCS expansion and potential PCM reduction promoted solute transport and osteocyte mechanosensing via primary cilia, but suppressed
mechanosensing via fluid shear and/or drag force on the cell membrane. Interestingly, loading at 2 or 4 Hz was found to overcome the
mechanosensing deficits observed at 0.5 Hz and these counter effects became more pronounced at 4 Hz and with sparser PCM in the lactating bone. Synergistically, higher loading frequency (2, 4 Hz) and sparser PCM enhanced flow-mediated
mechanosensing and diffusion/convection of nutrients and signaling molecules for osteocytes. In summary, lactation-induced structural changes alter the local environment of osteocytes in ways that favor metabolism, mechanosensing, and post-weaning recovery of maternal bone. Thus, osteocytes play a role in balancing the metabolic and mechanical functions of female skeleton during reproduction and lactation.