During the fracture healing process, osteoblasts and osteoclasts, as well as the nervous system are known to play important roles for signaling in the body. Glia cells contribute to the healing process by myelination, which can increase the speed of signals transmitted between neurons. However, the behavior of myelinating cells at a fracture site remains unclear. We developed a myelin protein zero (mpz)-EGFP transgenic medaka line for tracing myelinating cells. Mpz-enhanced green fluorescence protein (EGFP)-positive (mpz+) cells are driven by the 2.9-kb promoter of the medaka mpz gene, which is distributed throughout the nervous system, such as the brain, spinal cord, lateral line, and peripheral nerves. In the caudal fin region, mpz+ cells were found localized parallel with the fin ray (bone) in the adult stage. mpz+ cells were not distributed with fli-DsRed positive (fli+) blood vessels, but with some nerve fibers, and were dyed with the anti-acetylated tubulin antibody. We then fractured one side of the caudal lepidotrichia in a caudal fin of mpz-EGFP medaka and found a unique phenomenon, in that mpz+ cells were accumulated at 1 bone away from the fracture site. This mpz+ cell accumulation phenomenon started from 4 days after fracture of the proximal bone. Thereafter, mpz+ cells became elongated from the proximal bone to the distal bone and finally showed a crosslink connection crossing the fracture site to the distal bone at 28 days after fracture. Finally, the effects of rapamycin, known as a mTOR inhibitor, on myelination was examined. Rapamycin treatment of mpz-EGFP/osterix-DsRed double transgenic medaka inhibited not only the crosslink connection of mpz+ cells but also osterix+ osteoblast accumulation at the fracture site, accompanied with a fracture healing defect. These findings indicated that mTOR signaling plays important roles in bone formation and neural networking during fracture healing. Taken together, the present results are the first to show the dynamics of myelinating cells in vivo.

中文翻译：

---

髓鞘蛋白零 (p0) 转基因青鳉系骨折愈合过程中的髓鞘形成

在骨折愈合过程中，成骨细胞和破骨细胞以及神经系统在体内信号传递方面发挥着重要作用。神经胶质细胞通过髓鞘形成促进愈合过程，这可以增加神经元之间信号传输的速度。然而，骨折部位髓鞘形成细胞的行为仍不清楚。我们开发了髓鞘蛋白零 (mpz)-EGFP 转基因青鳉系，用于追踪髓鞘形成细胞。Mpz 增强型绿色荧光蛋白 (EGFP) 阳性 (mpz+) 细胞由 medaka mpz 基因的 2.9-kb 启动子驱动，该基因分布于整个神经系统，如大脑、脊髓、侧线和外周神经。在尾鳍区域，发现 mpz+ 细胞与成体阶段的鳍条（骨骼）平行。mpz+细胞不分布有fli-DsRed阳性（fli+）血管，而是分布有一些神经纤维，并用抗乙酰化微管蛋白抗体染色。然后，我们在 mpz-EGFP 青鳉的尾鳍中将尾纤毛的一侧骨折，并发现了一个独特的现象，即 mpz+ 细胞聚集在远离骨折部位的 1 块骨头上。这种 mpz+ 细胞积累现象从近端骨骨折后 4 天开始。此后，mpz+ 细胞从近端骨到远端骨拉长，最终在骨折后 28 天显示出穿过骨折部位到远端骨的交联连接。最后，检测了被称为 mTOR 抑制剂的雷帕霉素对髓鞘形成的影响。mpz-EGFP/osterix-DsRed 双转基因青鳉的雷帕霉素处理不仅抑制了 mpz+ 细胞的交联连接，而且抑制了骨折部位 osterix+ 成骨细胞的积累，并伴有骨折愈合缺陷。这些发现表明 mTOR 信号在骨折愈合过程中的骨形成和神经网络中起着重要作用。综上所述，目前的结果首次显示了体内髓鞘形成细胞的动态。