“We knew that Notch is important in patterning the skeleton,” said Dr. Brendan Lee, professor of molecular and human genetics and pediatrics at BCM and a Howard Hughes Medical Institute investigator. “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.”
“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.”
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 possiblity 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, said Lee, also a researcher in the Dan L. Duncan Cancer Center at BCM.
The work demonstrates the importance of going from patients to the laboratory and back again, he said. This study began with patients who suffer from a problem called spondylocostal dysplasia. These children and adults have problems with the pattern of their spine. They have fusions of parts of the spine or ribs. Several years ago, other scientists showed that a mutation of the pathway for Notch causes some of these problems. “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 also plays a role in other disorders, including those of the blood and cancer.
“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.”
That knowledge led him and his colleagues to look at the protein in bone.
“This is a complex system and it is why personalized medicine is important,” said Lee. “By identifying all of the major (cellular) pathways that contribute to a specific trait or feature like bone mass in each person, we could one day develop therapies specific for that person.”
Atomic-level motion may drive bacteria's ability to evade immune system defenses
24.04.2017 | Indiana University
Two-dimensional melting of hard spheres experimentally unravelled after 60 years
24.04.2017 | University of Oxford
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences