Department of Orthopaedic Surgery, Graduate School, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan.
Faculty of Medicine, Tokyo Medical and Dental University (TMDU), Tokyo, 113-8519, Japan.
Sci Rep. 2023 Mar 22;13(1):4674. doi: 10.1038/s41598-023-30492-4.
Bone is one of the largest organ systems in humans and is considered to regulate whole-body homeostasis in cooperation with other organs. We have previously reported that a sympathetic or sensory nervous system inside bone regulates bone homeostasis. However, the detailed regulatory mechanism, including the distribution of nerves inside bone, remains unknown. Although a two-dimensional histological analysis has been widely used to evaluate the structure of nerves or blood vessels, the actual structure is more complex, suggesting that it should be evaluated three-dimensionally. Here, we established a novel bone tissue clearing technique (Osteo-DISCO) for murine bones which enabled us to visualize the detailed distribution of nerves or blood vessels inside bone. Interestingly, we found that there is a specific nerve entry site in each long bone and that surgical ablation of the specific nerve fibers entering bone tissue led to decreased bone formation and impaired bone regeneration. Furthermore, we revealed that the administration of calcitonin gene-related peptide (CGRP), which is primarily released from sensory nerves, suppressed the bone loss caused by surgical nerve ablation. An in vitro study also indicated that CGRP directly promotes osteoblast activity, suggesting that sensory nerves inside bone can regulate osteogenesis via the secretion of CGRP.
骨骼是人体最大的器官系统之一，被认为与其他器官一起调节全身的稳态。我们之前曾报道过骨骼内的交感或感觉神经系统调节骨骼稳态。然而，包括骨骼内神经分布在内的详细调节机制仍不清楚。虽然二维组织学分析已广泛用于评估神经或血管的结构，但实际结构更为复杂，表明应进行三维评估。在这里，我们为鼠骨建立了一种新的骨组织透明化技术（Osteo-DISCO），使我们能够可视化骨骼内神经或血管的详细分布。有趣的是，我们发现每个长骨都有一个特定的神经进入部位，而手术消融进入骨组织的特定神经纤维会导致骨形成减少和骨再生受损。此外，我们揭示了降钙素基因相关肽（CGRP）的给药，CGRP 主要从感觉神经释放，可抑制手术神经消融引起的骨丢失。体外研究还表明，CGRP 直接促进成骨细胞活性，表明骨骼内的感觉神经可以通过分泌 CGRP 来调节成骨作用。
