Features of TMDU ResearchBone biology~Beyond the boundaries~
Tomoki Nakashima
Professor of Cell Signaling at TMDU

Q

Preosteoclast

Osteocyte

Osteoclast

You are conducting research on bone metabolism. Concerning hard tissues, which particularstudies are drawing attention, or leading theway, internationally? Of those studies, which
are you most interested in and possibly
working on ?

A: Bone is constantly renewed by the balanced action of boneformation and bone resorption, both of which mainly occur atthe bone surface. This restructuring process, called "boneremodeling", is important not only for normal bone mass andstrength, but also for mineral homeostasis and haematopoiesis.
An imbalance of bone remodeling is linked to various bonediseases. Furthermore, bone traditionally has been regarded
as a part of the skeletal and locomotor system, but recent
studies suggest that the skeletal system regulates systemic
biological functions based on the inseparable link between
the bone system and other systems, such as the endocrine
system. This systemic network is called the “osteonetwork”.
Using a genetic approach in mice, we established a newmethod for the isolation of high purity osteocytes. We
demonstrated that osteocytes embedded within the bonematrix are the commander cells at the initiation of bone
remodeling, through regulation of osteoclastogenesis (1).
Furthermore, we recently reported that the semaphorin
molecule Sema3A has a crucial role in the regulation of bone
remodeling. Sema3A that is derived from osteoblast lineage
cells, including osteocytes, inhibits osteoclast differentiationand promotes osteoblast differentiation synchronously toDr. Nakashima graduated from the Graduate
School of Pharmaceutical Science, Nagasaki
University. In 2002, he joined the Penninger
laboratory at the University of Toronto as
a postdoctoral fellow. In 2006, he joined
the Takayanagi laboratory at TMDU as an
Assistant Professor. In 2013, he became aPrincipal Investigator at the Graduate
School of Medical and Dental Sciences at TMDU.

14RANKLIn vitro osteoclastogenesis wasremarkably induced by osteocytes
increase bone mass. These studies provide a scientific basis for
future therapeutic approaches to bone diseases (2) .

Q

TMDU is known for scores of milestone R&D
results in dentistry. How is your research
related to this tradition?

A: TMDU is a distinguished institute and known as a world
center for the study of hard tissue biology for tooth and bonediseases. So, research and medicine at TMDU is critical for thefuture welfare of the human race, and is of particular importance in Japan, the world's most rapidly aging society.

Q

What do you expect from your future projects?

A: We have been studying the mechanism of bone remodeling, intracellular signal transduction and the source of RANKLin the context of osteoclastogenesis. Our recent studies haveidentified the molecules mediating the communication amongcells in bone (3) . A molecular-level understanding of the osteonetwork will provide a novel framework for understanding
the bone and systemic systems as well as a molecular basis fordeveloping new strategies against various diseases.
1) Evidence for osteocyte regulation of bone homeostasis through RANKL
expression, Nat Med., doi:10.1038/nm.2452.
2) Osteoprotection by semaphorin3A, Nature., doi: 10.1038/nature11000.
3) New insights into osteoclastogenic signaling mechanisms, Trends EndocrinolMetab., doi: 10.1016/j.tem.2012.05.005.