Harnessing the beneficial effects of exercise on bone to create new therapies for osteoporosis

4 August 2020

Researchers at AMBER, the SFI Research Centre for Advanced Materials and Bioengineering Research and the Schools of Engineering and Pharmacy at Trinity College Dublin, have shed new light on the role of exercise on bone growth. Their work has opened the door to potential new therapies for bone diseases such as osteoporosis.

The team discovered that when bone cells (osteocytes) are subjected to physical loading, similar to that experienced during exercise, they produce signals causing human bone marrow stem cells to grow new bone. This mechanism can be functionalised to create new therapeutic approaches to bone diseases which affect millions of people globally.

Bone growth, osteoporosis and exercise

Around 300,000 people in Ireland have osteoporosis and many more may live with the disease undetected. It can be particularly problematic as we get older when bone regeneration becomes slower.

One in 4 men and 1 in 2 women over 50 will develop a fracture due to osteoporosis in their lifetime, according to the Irish Osteoporosis Society. The cost of care for these patients is high, as many require hospitalisation and surgery, with an estimated total cost of care of €653 million. Finding new ways to treat these diseases will have considerable impact on patients and hospitals.

While it is well known that exercise – particularly weight bearing/strengthening exercise – supports bone health, in conjunction with other factors, the specific mechano-biological pathway explaining this relationship has remained elusive.

Cellular level insights into the impact of exercise on bone growth

The Trinity team found that when osteocytes are subjected to a physical load mimicking exercise they release nano-sized vesicles that enhance bone marrow stem cell differentiation, and promote bone formation.

Key to this study, and the possibility to advance therapeutic approaches based on this mechanism, was the teams’ discovery of the precise role of the vesicles in the process of bone generation.

The vesicles, when generated by osteocytes under physical loading, act as a communication mechanism, carrying information from osteocytes to bone marrow stem cells. The chemicals inside the vesicles tell bone marrow stem cells to turn into cells fundamental to the process of bone generation. This communication mechanism holds great potential to act as a novel, cell‐free, therapy to enhance bone regeneration.

The Trinity team recently published their findings in the high-profile journal Stem Cells Translational Medicine.

Professor David Hoey, Trinity’s School of Engineering, said:

“This work highlights the importance of considering physical factors in biology and medicine, demonstrating an interesting example of where mechanics alone was sufficient to change cell behaviour, and in this case, support bone growth. This gives us significant insight into the role of exercise in bone formation and specifically intra-cellular communication.

“This work identified that mechanically activated vesicles can be harnessed to promote stem cell differentiation in the lab. Harnessing these small vesicles we hope to develop new therapies for bone regeneration that mimic the beneficial effects of exercise on bone, potentially transforming how millions suffering from osteoporosis and bone defects are treated each year. Our next step is to test their efficacy in pre-clinical models.”

This work was conducted in collaboration with Professor Lorraine O’Driscoll from Trinity’s School of Pharmacy. It was funded by the Irish Research Council, the European Research Council and Science Foundation Ireland.