Hara-Irie F, Amizuka N, Ozawa H
Department of Oral Anatomy, Niigata University School of Dentistry, Japan.
Bone. 1996 Jan;18(1):29-39. doi: 10.1016/8756-3282(95)00425-4.
We performed immunohistochemical and ultrastructural studies to disclose a possible relationship between nerve fibers and bone metabolism. Immunohistochemical distribution of calcitonin gene-related peptide (CGRP)-positive nerve fibers during bone development was assessed in the femurs of rats. CGRP-positive nerve fibers were denser in the epiphysis than in the metaphysis. These nerve fibers particularly ran along the epiphyseal trabecules facing the growth plate and came in contact with osteoclasts. Many osteoclasts at the epiphyseal trabecules facing the growth plate contained abundant toluidine blue and periodic acid-Schiff-positive granules. Electron microscopy revealed that these osteoclasts have many membrane-bound, electron-dense granular structures and dilated cisterns of rough endoplasmic reticulum containing electron-dense material. They were often surrounded by clear cells displaying features of nerve fiber and had no ruffled border. Furthermore, ultrastructural observations revealed electron-dense structures coating the cytoplasmic side of plasma membranes of the nerve fibers. We also observed coated pits in the cytoplasm of the osteoclasts facing the nerve fibers. To further clarify the role of innervation, we compared trabecules of rats undergoing denervation of the sciatic nerve with those from unoperated rats. Denervation resulted in a significant increase in the number of cement lines on the epiphyseal trabecules facing the growth plate. These results suggest that the osteoclasts at the epiphyseal trabecules facing the growth plate are in part regulated by CGRP-positive nerve fibers. Thus, CGRP-positive nerve fibers could be a crucial element in bone metabolism during bone growth and development.
我们进行了免疫组织化学和超微结构研究，以揭示神经纤维与骨代谢之间可能存在的关系。在大鼠股骨中评估了骨发育过程中降钙素基因相关肽（CGRP）阳性神经纤维的免疫组织化学分布。CGRP阳性神经纤维在骨骺处比干骺端更密集。这些神经纤维尤其沿着面向生长板的骨骺小梁走行，并与破骨细胞接触。在面向生长板的骨骺小梁处，许多破骨细胞含有丰富的甲苯胺蓝和过碘酸希夫阳性颗粒。电子显微镜显示，这些破骨细胞有许多膜结合的、电子致密的颗粒结构以及含有电子致密物质的扩张的粗面内质网池。它们常被显示出神经纤维特征的透明细胞所包围，且没有皱褶缘。此外，超微结构观察显示，神经纤维质膜的胞质侧有电子致密结构。我们还在面向神经纤维的破骨细胞胞质中观察到了有被小窝。为了进一步阐明神经支配的作用，我们将坐骨神经去神经支配的大鼠的小梁与未手术大鼠的小梁进行了比较。去神经支配导致面向生长板的骨骺小梁上的黏合线数量显著增加。这些结果表明，面向生长板的骨骺小梁处的破骨细胞部分受CGRP阳性神经纤维调节。因此，CGRP阳性神经纤维可能是骨骼生长发育过程中骨代谢的关键因素。
