Local disruption of the canalicular network in ageing human bone

Bone remodelling is regulated by osteocytes and occurs through complementary functions of bone building and bone resorbing cells, osteoblasts and osteoclasts. Osteocytes are enclosed in lacunae interconnected via an extended 3D network of canaliculi to form the osteocyte lacuno-canalicular network (OLCN), crucial to maintaining mineralised bone homeostasis. Loss of bone strength and bone mineral density occurs with ageing, possibly related to an observed deterioration of network connectivity leading to an altered fluid flow through the OLCN, shown to be a regulator of the bone remodelling process. We propose to investigate OLCN network distortions using synchrotron X-Ray nano-holotomography (SR XNH) in osteons of healthy individuals of different age and in samples from patients carrying a mutation affecting the OLCN. The possibility of resolving single canaliculi will provide insight into the deterioration process of the OLCN, a possible contributor of age-related bone loss.

骨重建受骨细胞调控，通过成骨细胞与破骨细胞的协同功能完成骨形成与骨吸收过程。骨细胞被包裹于骨陷窝中，并通过延伸的三维骨小管网络相互连接，形成骨细胞陷窝-小管网络（osteocyte lacuno-canalicular network, OLCN），该网络对维持矿化骨稳态至关重要。随年龄增长，骨骼强度与骨密度会出现丢失，这可能与已观测到的网络连通性退化相关：连通性退化会改变流经OLCN的流体流动，而流体流动已被证实是骨重建过程的调控因子。本研究拟采用同步辐射X射线纳米断层扫描（synchrotron X-Ray nano-holotomography, SR XNH）技术，对不同年龄段健康个体的骨单位以及携带影响OLCN突变患者的样本开展OLCN网络畸变相关研究。该技术可实现单根骨小管的分辨成像，有助于深入解析OLCN的退化进程，而该进程可能是年龄相关性骨丢失的潜在诱因。