Protein ‘Notch’ Found To Strengthen Bone Formation

by Dr. Sunil Shroff on  February 26, 2008 at 4:04 PM Research News   - G J E 4
Protein ‘Notch’ Found To Strengthen Bone Formation
A protein called Notch was identified by researchers from Baylor College of Medicine in Houston. Notch, which helps in determining cell differentiation into different kinds of tissues in embryos also helps in bone formation and bone strength in later years.

The results of this study, led by Dr. Brendan Lee, professor of molecular and human genetics and pediatrics at BCM and a Howard Hughes Medical Institute investigator, may act as a base for understanding osteoporosis and also in diseases in which there is too much bone.

"We knew that Notch is important in patterning the skeleton. 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. Notch stimulates early proliferation of osteoblastic cells (cells responsible for bone formation). However, when they 'knocked out' the Notch function in such cells in the laboratory, they found osteoporosis or the loss of bone, similar to age-related osteoporosis in humans," Nature Medicine quoted Lee, as saying.

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

When the researchers abolished Notch function in bone forming cells, it was found that the osteoblasts, which advance bone formation, worked properly. But, the animals were not able to regulate activity of osteoclasts, whose primary function is to resorb or remove bone.

Those women that suffer from osteoporosis actually have a similar problem—an imbalance of bone formation vs. bone resorption. They are able to produce enough bone but the resorbtion of bone cells is at an abnormally high rate.

In their experiment, it was discovered that when animals were raised to be short of Notch, they also lost also the ability to suppress bone resorption. This balance between bone formation and resorption makes it possible for the organisms to maintain a healthy skeleton.

Experiments in future may examine the prospect that loss of Notch interferes with the natural signal between osteoblasts and osteoclasts (bone resorbing cells) and also thwarts the homeostasis or natural balance between the two.

According to Lee, this implies that the protein Notch and the cellular pathways that express and control it might aim for drugs to treat bone disorders.

"Our care of these patients suggested to us that Notch may have important function even after the establishment of this initial pattern of the skeleton. Notch is important in the blood system," said Lee. "It regulates whether a stem cell becomes a 'T' or a 'B' cell. When Notch is mutated in the blood system, it causes cancer," said Lee.

The study has appeared online in the journal Nature Medicine.

Source: ANI

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