What is your objective?

What is your image of bone? A hard, white block of calcium... Something like a "skeleton" is the sort of inorganic image most people have. But in reality, bones are a living organ full of vitality and containing large amounts of living cells.
There are three types of bone cell: 1. Osteoblasts, which create bone; 2. Osteoclasts, which destroy bone; and 3. Osteocytes, which are buried in bone. This third type, the osteocyte, accounts for 90% or more of the cells in bone. So what do these large amounts of bone-buried osteocytes do? Actually, they sense gravity and movement activity.

Figure 1  Bone-buried osteocytes 

Osteocytes have a large number of projections that reach out like hands and link together to create a neuron-like network formation inside the solid bones (Figure 1). Through this network formation, osteocytes can sense our movement activity and gravity (mechanical stress), and can not only give signals to the osteoblasts and osteoclasts to remodel the bone, but, as has been discovered recently, can even control immune tissue such as the thymus and white adipose tissue.
The bone, which is equipped with osteocytes, is a sensory organ. We are conducting research to discover what effect the bone as a sensory organ has on the whole body.

 

What sort of experiments are you conducting?

Figure 2  Bone cell lines and students performing experiments

If the bone is like other sensory organs such as the eyes, ears, and nose, it may have similar functions to relay gravity and movement stimuli to the brain and other organs as nerve stimuli. If osteocytes take a central role in this function, they may produce neurotransmitters and stimulate peripheral nerves spread throughout bone. We utilize bone cell lines such as osteoblastic cell lines, osteocytic cell lines, chondrocytic cell lines and bone marrow stromal cell lines to analyze whether mechanical stress changes the expression of neurotransmitters at the mRNA and protein level (Figure 2). We are also using bones derived from mice exposed to various stimuli to check for changes in nerve formation or neurotransmitter expression. Furthermore, to examine the ways in which osteocytes regulate remote organs other than through nerve signals, we focus on the “microvesicle”. Microvesicles are small particles that contain various molecules and secreted various cells. We found that osteocytes produce microvesicles containing microRNA and other small RNA molecules. We speculated that mechanical stress may upregulate the production of microvesicles by osteocytes and that osteocytes may deliver microvesicles to remote organs through the blood and regulate these organs through the microRNA included in the microvesicle. To examine this hypothesis, we analyzed changes in small RNA expression in microvesicles isolated from the serum of mice with damaged osteocytes or osteocytic cell lines.

 

What do you enjoy about doing research?

Scientific research often expands not only our scientific vision but also our life. Through my previous study, I obtained new knowledge about the whole body and realized that the human body is full of mystery! Furthermore, it is an amazing experience when my study impresses not only other researchers but also the general public and changes their values or life. This can happen through outreach activities such as presentations at scientific meeting and events, in the printed media, or on television (Figures 4, 5). I want to continue with the challenge of uncovering new regulatory mechanisms in the human body through bone research.

Figure 4  With the female winners of the Hokkaido University Otsuka Award for researchers Figure 5  Recording for TV

 

References

(1)     Sato, Mari et al., "Multi-Organ Control by Bone Cells (Kotsusaibou ni yoru tazouki seigyo)" THE BONE, Medical Review Co., Ltd.

27(3): 71-75 (2013)