Department of Physical Therapy, University of Delaware, Newark, DE, USA.
J Bone Miner Res. 2011 Mar;26(3):618-29. doi: 10.1002/jbmr.236.
Osteocytes project long, slender processes throughout the mineralized matrix of bone, where they connect and communicate with effector cells. The interconnected cellular projections form the functional lacunocanalicular system, allowing fluid to pass for cell-to-cell communication and nutrient and waste exchange. Prevention of mineralization in the pericellular space of the lacunocanalicular pericellular space is crucial for uninhibited interstitial fluid movement. Factors contributing to the ability of the pericellular space of the lacunocanalicular system to remain open and unmineralized are unclear. Immunofluorescence and immunogold localization by transmission electron microscopy demonstrated perlecan/Hspg2 signal localized to the osteocyte lacunocanalicular system of cortical bone, and this proteoglycan was found in the pericellular space of the lacunocanalicular system. In this study we examined osteocyte lacunocanalicular morphology in mice deficient in the large heparan sulfate proteoglycan perlecan/Hspg2 in this tissue. Ultrastructural measurements with electron microscopy of perlecan/Hspg2-deficient mice demonstrated diminished osteocyte canalicular pericellular area, resulting from a reduction in the total canalicular area. Additionally, perlecan/Hspg2-deficient mice showed decreased canalicular density and a reduced number of transverse tethering elements per canaliculus. These data indicated that perlecan/Hspg2 contributed to the integrity of the osteocyte lacunocanalicular system by maintaining the size of the pericellular space, an essential task to promote uninhibited interstitial fluid movement in this mechanosensitive environment. This work thus identified a new barrier function for perlecan/Hspg2 in murine cortical bone.
骨细胞在矿化基质中伸出长而细的突起，与效应细胞相连并进行通讯。相互连接的细胞突起形成功能性的骨陷窝-小管系统，允许液体通过以进行细胞间通讯和营养物质及废物交换。防止细胞外基质中的矿化对于无抑制的细胞间液流动至关重要。目前尚不清楚哪些因素有助于保持骨陷窝-小管系统细胞外基质的开放和非矿化状态。免疫荧光和透射电子显微镜免疫金定位显示，核心蛋白聚糖/perlecan（Hspg2）信号定位于皮质骨的骨细胞陷窝-小管系统，该蛋白聚糖存在于骨陷窝-小管系统的细胞外基质中。在这项研究中，我们研究了在这种组织中缺乏大型肝素硫酸蛋白聚糖核心蛋白聚糖/perlecan（Hspg2）的小鼠的骨细胞陷窝-小管形态。对核心蛋白聚糖/perlecan（Hspg2）缺陷小鼠进行超微结构测量和电子显微镜观察，结果显示，由于总小管面积减少，骨细胞小管细胞外基质面积减小。此外，核心蛋白聚糖/perlecan（Hspg2）缺陷小鼠的小管密度降低，每个小管的横向连接元素数量减少。这些数据表明，核心蛋白聚糖/perlecan（Hspg2）通过维持细胞外基质的大小来维持骨细胞陷窝-小管系统的完整性，这是促进这种机械敏感环境中无抑制的细胞间液流动的一项重要任务。因此，这项工作在小鼠皮质骨中确定了核心蛋白聚糖/perlecan（Hspg2）的一个新的屏障功能。
