Another notch in the pathway

Source: Baylor College of Medicine

Notch, a protein known to govern the determination of cell differentiation into different kinds of tissues in embryos, plays a critical role in bone formation and strength later in life, Baylor College of Medicine researchers have found.

Reporting in Nature Medicine, the researchers said their findings may provide a basis for understanding osteoporosis and in diseases in which there is too much bone.

"We knew that Notch is important in patterning the skeleton," senior author Dr Brendan Lee, professor of molecular and human genetics and paediatrics at BCM, said. "After this initial patterning of the skeleton, we saw a dimorphic or two-pronged function for Notch. If there was an increase of Notch activity in bone cells, we get a lot more bone."

Lee said Notch stimulates early proliferation of osteoblastic cells. However, when Notch function is knocked out if led to osteoporosis or the loss of bone, similar to age-related osteoporosis in humans."

"Mice had an acceptable amount of bone at birth, but as they got older, they lost more and more bone," Lee said. "Loss of Notch signaling might relate to what happens when we get older."

They found that the osteoblasts, which promote bone formation, worked fine when they abolished Notch function in bone forming cells. However, the animals lacked the ability to regulate activity of osteoclasts, whose primary function is to resorb or remove bone.

Many women who have osteoporosis actually have a similar problem, an imbalance of bone formation vs. bone resorption. They make enough bone but they resorb bone cells at an abnormally high rate.

In the laboratory, Lee and his colleagues found that when animals were bred to lack Notch, they lost also the ability to suppress bone resorption. That balance between bone formation and resorption allows organisms to maintain a healthy skeleton.

Future studies may look at the possibility that loss of Notch interferes with the natural signal between osteoblasts and osteoclasts (bone resorbing cells) and prevents the homeostasis or natural balance between the two.

That means the protein Notch and the cellular pathways that express and control it might be targets for drugs to treat bone disorders, Lee said.