Irish scientists have shed new light on why exercise boosts bone growth, which has opened the door to potential new therapies for debilitating bone diseases such as osteoporosis.
When bone cells, known as 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, a team based at Trinity College Dublin have established.
“This mechanism can be functionalised to create new therapeutic approaches to bone diseases which affect millions of people globally,” they concluded.
About 300,000 people in Ireland have osteoporosis, which causes bones to become weak and brittle, while many more may live with the disease undetected. It can be particularly problematic as people get older when bone regeneration becomes slower.
One in four men and one in two women over 50 will develop a fracture due to osteoporosis in their lifetime, according to the Irish Osteoporosis Society. Cost of care is high, as many require hospitalisation and surgery, with an estimated total cost of care of €653 million annually.
A 2013 paper outlined 18,000 osteoporotic fractures occur every year in Ireland, so finding new ways to treat these diseases will have considerable impact on patients and hospitals.
"While it is well known 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," explained Prof David Hoey of TCD school of engineering.
When osteocytes are subjected to a physical load mimicking exercise they release tiny nano-sized vesicles that enhance bone marrow stem cell differentiation, and promote bone formation, the team found.
The research was a collaboration with Prof Lorraine O’Driscoll at the school of pharmacy and AMBER, the SFI Research Centre for Advanced Materials and Bioengineering Research, and published in the journal Stem Cells Translational Medicine.
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, Prof Hoey added.
The vesicles 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, therapy to enhance bone regeneration. “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 provides significant insight into the role of exercise in bone formation and specifically intra-cellular communication as it means 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,” he confirmed.