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Elucidation of Bone Regeneration Mechanism


News provided by

Tokyo Institute of Technology

Nov 02, 2017, 12:00 ET

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TOKYO, Nov. 2, 2017 /PRNewswire/ -- Fish have the extraordinary ability to regenerate lost fins and other appendages containing cartilage and bone. The cells responsible for the regeneration offer new clues on how to regenerate tissues in humans. Researchers at Tokyo Institute of Technology (Tokyo Tech) have found a dormant progenitor cell population in zebrafish that regenerates bone cells, or osteoblasts. The study can be read in Developmental Cell.

OPC in the niche of fin joint:  OPCs marked in green, osteocyte-lineage marker, Zns5, in red, and cell nuclei in blue.  OPCs that are dormant in the niche have a unique shape with dendrites.
OPC in the niche of fin joint: OPCs marked in green, osteocyte-lineage marker, Zns5, in red, and cell nuclei in blue. OPCs that are dormant in the niche have a unique shape with dendrites.

How osteoblasts are supplied during bone regeneration has been controversial among bone researchers. According to Atsushi Kawakami, an Associate Professor who specializes in tissue regeneration and led the study, scientists disagree on how these cells are made.

The new study uses genetically engineered transgenic zebrafish to show that a population of progenitor cells marked by high expression of matrix metalloproteinase 9, an enzyme that catabolizes collagens, provides osteoblasts during regeneration. Kazunori Ando, a graduate student who conducted the experiments, calls these cells osteoblast progenitor cells (OPCs). Consistently, eliminating OPCs prior to tissue injury significantly impaired bone regeneration. Overall, the study shows that OPCs are essential for bone regeneration.

The researchers further investigated the developmental origin of OPCs and found that OPCs are derived from embryonic somites and reserved in niches of bone-forming tissues in adult animal as the source of osteoblasts. Embryonic somites produce osteoblasts during vertebrate development, but its relationship to adult osteoblasts was not known. The study revealed that OPCs derived from the somites are the dormant cells for later production of osteoblasts in adult animal. 

In conclusion, the findings suggest that a lineage of bone-producing cell, which are specified in  embryonic somites, are maintained throughout the animal lives as progenitor cells for bone regeneration and also for bone maintenance.  

"We use animal models because they show us a number of essential cellular and molecular mechanisms behind our existence. Considering the higher bone regeneration potential in zebrafish, OPCs will be a potential target for enhancing bone regeneration in mammals" said Kawakami.

Reference

Kazunori Ando1, Eri Shibata1, Stefan Hans2, Michael Brand2, Atsushi Kawakami1, *, Osteoblast Production by Reserved Progenitor Cells in Zebrafish Bone Regeneration and Maintenance, Developmental Cell, DOI: 10.1016/j.devcel.2017.10.015

1 School of Life Science and Technology, Tokyo Institute of Technology
2 Developmental Genetics, DFG-Center for Regenerative Therapies Dresden

About Tokyo Institute of Technology

Tokyo Institute of Technology stands at the forefront of research and higher education as the leading university for science and technology in Japan. Tokyo Tech researchers excel in a variety of fields, such as material science, biology, computer science and physics. Founded in 1881, Tokyo Tech has grown to host 10,000 undergraduate and graduate students who become principled leaders of their fields and some of the most sought-after scientists and engineers at top companies. Embodying the Japanese philosophy of "monotsukuri," meaning technical ingenuity and innovation, the Tokyo Tech community strives to make significant contributions to society through high-impact research. http://www.titech.ac.jp/english/

SOURCE Tokyo Institute of Technology

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