“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.”
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22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
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