Scientists have discovered that calcium, the main constituent of our bones, plays a crucial role in turning undifferentiated stem cells in the very early embryo into bone cells. These findings could lead to treatment for people who suffer from limited craniofacial bone growth, such as those affected by a congenital disease known as Treacher Collins Syndrome (TCS).
Roughly one in 50,000 babies are born with this disorder in Europe. It is characterised by the fact that patients do not form the neural crest cells from which the jaw, inner ears and other bones in the head develop. This means that they suffer from severe craniofacial deformities and have to go through many reconstructive facial surgeries as children, as well as trachea surgery to be able to breath normally.
In a study published in the journal Cell, researchers led by Michael Rape from the University of Berkeley focused on identifying key molecular signals that trigger proper bone growth in the hope of getting the inspiration to find treatments that will allow patients to avoid painful facial surgery.
Switching proteins on
The team had in the past identified enzymes that allowed embryos' undifferentiated stem cells to develop into neural crest cells. Indeed, they had shown that an enzyme called CUL3 drives a process that combines two proteins - ubiquitin and TCOF1 - to make stem cells turn into neural crest cells.
The idea that properly functioning CUL3 enzymes are necessary to form the cells that will develop into craniofacial bones was thus at the centre of their new study. With a series of experiments, the team discovered that calcium was needed for CUL3 to become activated and functional.
"Our research basically identifies calcium not only as a structural element of bone, which makes the bone strong and sturdy, but also as a signalling molecule for bone formation that we hadn't appreciated before, which can be used to turn enzymes on and off. Calcium is a very important regulatory molecule that allows the organism to make cell-fate decisions," Rape explains.
This discovery could pave the way for new treatment research. For instance, using calcium to stimulate bone growth may be an interesting option, but more studies will be needed before attempting these regenerative therapies.
However, Rape's team is now even more determined to succeed after meeting and spending time with University of Colorado researcher Francis Smith, who suffers from Treacher Collins Syndrome, as it showed them their findings have a concrete significance for patients.