2. Academic Validation
  3. Myelination during fracture healing in vivo in myelin protein zero (p0) transgenic medaka line

Myelination during fracture healing in vivo in myelin protein zero (p0) transgenic medaka line

  • Bone. 2020 Apr;133:115225. doi: 10.1016/j.bone.2020.115225.
Yusuke Dodo 1,  Masahiro Chatani 2,  Yuki Azetsu 3,  Masahiro Hosonuma 4,  Akiko Karakawa 3,  Nobuhiro Sakai 3,  Takako Negishi-Koga 5,  Mayumi Tsuji 6,  Katsunori Inagaki 7,  Yuji Kiuchi 6,  Masamichi Takami 3
Affiliations

Affiliations

  • 1 Department of Pharmacology, Division of Medical Pharmacology, Showa University School of Medicine, Tokyo 142-8555, Japan; Department of Pharmacology, Showa University School of Dentistry, Tokyo 142-8555, Japan; Pharmacological Research Center, Showa University, Tokyo 142-8555, Japan; Department of Orthopaedic Surgery, Showa University School of Medicine, Tokyo 142-8555, Japan.
  • 2 Department of Pharmacology, Showa University School of Dentistry, Tokyo 142-8555, Japan; Pharmacological Research Center, Showa University, Tokyo 142-8555, Japan. Electronic address: chatani@dent.showa-u.ac.jp.
  • 3 Department of Pharmacology, Showa University School of Dentistry, Tokyo 142-8555, Japan; Pharmacological Research Center, Showa University, Tokyo 142-8555, Japan.
  • 4 Department of Pharmacology, Division of Medical Pharmacology, Showa University School of Medicine, Tokyo 142-8555, Japan; Department of Pharmacology, Showa University School of Dentistry, Tokyo 142-8555, Japan; Pharmacological Research Center, Showa University, Tokyo 142-8555, Japan.
  • 5 Department of Pharmacology, Showa University School of Dentistry, Tokyo 142-8555, Japan; Pharmacological Research Center, Showa University, Tokyo 142-8555, Japan; Division of Mucosal Barriology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
  • 6 Department of Pharmacology, Division of Medical Pharmacology, Showa University School of Medicine, Tokyo 142-8555, Japan; Pharmacological Research Center, Showa University, Tokyo 142-8555, Japan.
  • 7 Department of Orthopaedic Surgery, Showa University School of Medicine, Tokyo 142-8555, Japan.
PMID: 31923703 DOI: 10.1016/j.bone.2020.115225
Abstract

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.

Keywords

Bone fracture healing; Medaka; Myelination; mpz transgenic line.

Figures
Products