New mechanism helps bone cells regenerate in fractures

Researchers from Belgium have discovered a mechanism for the better survival of implanted cells that improves in the healing of bone fractures.

The bone cells, which earlier had dim chances of survival because of not being prepared for lack of oxygen and nutrients at the fracture site, can survive better by being preconditioned to withstand the adverse environment before the implantation process, said the researchers from KU Leuven University.

"Reprogramming the bone cells obtained from patients might increase their survival rate from 30 percent to 60 percent, which will ultimately lead to better bone regeneration," said Geert Carmeliet, professor at the University.

The researchers, in the experiment conducted on mice, managed to switch on a survival mode in bone cells by inactivating the oxygen sensor in the bone cells before implantation.

As a result, the bone cells started increasing the storage of an emergency fuel in the form of glycogen, which is in fact a sugar reservoir.

In addition, the bone cells also started using glutamine -- an amino acid -- to produce more antioxidants to neutralise the increased production of harmful oxygen radicals.

"These two adjustments allow bone cells to be self-supporting in terms of energy generation and to protect themselves against an increased level of oxygen radicals," Steve Stegen, doctoral student.

The study, published in the journal Cell Metabolism, showed that often, only 30 percent of the implanted bone cells survived the first few days. A major reason being that the blood vessels around the fracture, which deliver oxygen and nutrients to the cells, are starved for lack of oxygen and nutrients.

"The starved bone cells produce harmful oxygen radicals and thereby disturb the natural balance between antioxidants and oxygen radicals. An excess of these oxygen radicals causes irreversible cell damage," Carmeliet added.

Researchers tested in mice as to how they could better equip the bone cells for the crucial stage between implantation and ingrowth of the blood vessels, where the ingrowth of new blood vessels into the implant takes time and until then, the cells are out of fuel since oxygen and nutrient supply is insufficient, leading to the death of bone cells.