Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Proteins Causing Daytime Sleepiness Also Tied to Bone Formation

Published: Saturday, June 14, 2014
Last Updated: Saturday, June 14, 2014
Bookmark and Share
Orexin proteins provide target for osteoporosis, UT Southwestern researchers find.

Orexin proteins, which are blamed for spontaneous daytime sleepiness, also play a crucial role in bone formation, according to findings by UT Southwestern Medical Center researchers. The findings could potentially give rise to new treatments for osteoporosis, the researchers say.

Orexins are a type of protein used by nerve cells to communicate with each other. Since their discovery at UT Southwestern more than 15 years ago, they have been found to regulate a number of behaviors, including arousal, appetite, reward, energy expenditure, and wakefulness. Orexin deficiency, for example, causes narcolepsy - spontaneous daytime sleepiness. Thus, orexin antagonists are promising treatments for insomnia, some of which have been tested in Phase III clinical trials.

UT Southwestern researchers, working with colleagues in Japan, now have found that mice lacking orexins also have very thin and fragile bones that break easily because they have fewer cells called osteoblasts, which are responsible for building bones.

“Osteoporosis is highly prevalent, especially among post-menopausal women. We are hoping that we might be able to take advantage of the already available orexin-targeting small molecules to potentially treat osteoporosis,” said Dr. Yihong Wan, Assistant Professor of Pharmacology, the Virginia Murchison Linthicum Scholar in Medical Research, and senior author for the study, published in the journal Cell Metabolism.

Osteoporosis, the most common type of bone disease in which bones become fragile and susceptible to fracture, affects more than 10 million Americans. The disease, which disproportionately affects seniors and women, leads to more than 1.5 million fractures and some 40,000 deaths annually. In addition, the negative effects impact productivity, mental health, and quality of life. One in five people with hip fractures, for example, end up in nursing homes.

Orexins seem to play a dual role in the process: they both promote and block bone formation. On the bones themselves, orexins interact with another protein, orexin receptor 1 (OX1R), which decreases the levels of the hunger hormone ghrelin. This slows down the production of new osteoblasts and, therefore, blocks bone formation locally.

At the same time, orexins interact with orexin receptor 2 (OX2R) in the brain. In this case, the interaction reduces the circulating levels of leptin, a hormone known to decrease bone mass, and thereby promotes bone formation. Therefore, osteoporosis prevention and treatment may be achieved by either inhibiting OX1R or activating OX2R.

“We were very intrigued by this yin-yang-style dual regulation,” said Dr. Wan, a member of the Cecil H. and Ida Green Center for Reproductive Biology Sciences and UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center. “It is remarkable that orexins manage to regulate bone formation by using two different receptors located in two different tissues.”

The central nervous system regulation through OX2R, and therefore promotion of bone formation, was actually dominant over regulation through OX1R. So when the group examined mice lacking both OX1R and OX2R, they had very fragile bones with decreased bone formation. Similarly, when they assessed mice that expressed high levels of orexins, those mice had increased numbers of osteoblasts and enhanced bone formation.

The research was done in collaboration with Dr. Masashi Yanagisawa, Adjunct Professor of Molecular Genetics at UT Southwestern, a Howard Hughes Medical Institute investigator, and now with the International Institute for Integrative Sleep Medicine at the University of Tsukuba, in Japan. Dr. Yanagisawa’s laboratory discovered orexins in 1998.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More Than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Regenerative Medicine Biologists Discover a Cellular Structure that Explains Fate of Stem Cells
The findings are presented in the journal Nature.
Thursday, July 02, 2015
Cell that Replenishes Heart Muscle Found by UT Southwestern Researchers
Researchers devise a new cell-tracing technique to detect cells that do replenish themselves.
Tuesday, June 23, 2015
Researchers Find Molecular Mechanisms within Fetal Lungs that Initiate Labor
Biochemists found that steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2) proteins control genes.
Tuesday, June 23, 2015
Researchers Discover Molecule that Accelerates Tissue Regeneration
Newly discovered molecule, SW033291 accelerate cell recovery following bone marrow transplants.
Friday, June 12, 2015
Boosting Gut Bacteria Defense System May Lead to Better Treatments
Life-threatening bloodstream infections reversed by enhancing a specific immune defense response.
Tuesday, June 09, 2015
Immunity Enzyme Defends Against Tuberculosis Infection
Study shows that cGAS enzyme is essential for defense against the tuberculosis bacteria.
Wednesday, June 03, 2015
UT Southwestern Faculty Members Named HHMI Investigators
Appointment of Dr. Kim Orth and Dr. Joshua Mendell to HHMI.
Saturday, May 23, 2015
UT Southwestern’s Dr. Philipp Scherer Receive Banting Medal
Dr. Scherer will receive the prestigious Medal for diabetes research.
Friday, May 08, 2015
Mutations in Two Genes Linked to Familial Pulmonary Fibrosis and Telomere Shortening
PARN and RTEL1 genes strengthen the link between lung fibrosis and telomere dysfunction.
Tuesday, May 05, 2015
Scientists Identify Key Receptors Behind Development of AML
Blocking ITIM-receptor signaling in combination with conventional therapies may represent a novel strategy for AML treatment.
Saturday, May 02, 2015
Scherer to Receive Banting Medal for Diabetes Research
Medal recognizes significant, long-term contributions to the understanding, treatment, or prevention of diabetes.
Thursday, April 30, 2015
Study Reveals Molecular Genetic Mechanisms Driving Breast Cancer Progression
The findings are published online and in the journal Molecular Cell.
Saturday, April 04, 2015
New Cyclotron Facility at UT Southwestern
Expands research opportunities and imaging capabilities for detecting, tracking cancer.
Friday, March 20, 2015
Acetate Supplements Shown to Speed Up Cancer Growth
A major compound produced in the gut by host bacteria.
Friday, February 20, 2015
MAGE Genes Provide Insight into Optimizing Chemotherapy
UT Southwestern Medical Center scientists have identified a new biomarker that could help identify patients who are more likely to respond to certain chemotherapies.
Tuesday, February 17, 2015
Scientific News
Study Finds Brain Chemicals that Keep Wakefulness in Check
Researchers to develop new drugs that promote better sleep, or control hyperactivity in people with mania.
Sorting Through Cellular Statistics
Aaron Dinner, professor in chemistry, and his graduate student Herman Gudjonson are trying to read the manual of life, DNA, as part of the Dinner group’s research into bioinformatics—the application of statistics to biological research.
Playing 'Tag' with Pollution lets Scientists See Who's It
Using a climate model that can tag sources of soot from different global regions and can track where it lands on the Tibetan Plateau, researchers have determined which areas around the plateau contribute the most soot — and where.
Women’s Immune System Genes Operate Differently from Men’s
A new technology reveals that immune system genes switch on and off differently in women and men, and the source of that variation is not primarily in the DNA.
Long Telomeres Associated with Increased Lung Cancer Risk
Genetic predisposition for long telomeres predicts increased lung adenocarcinoma risk.
First Artificial Ribosome Designed
Researchers at the University of Illinois at Chicago and Northwestern University have engineered a tethered ribosome that works nearly as well as the authentic cellular component, or organelle, that produces all the proteins and enzymes within the cell.
High-Resolution 3D Images Reveal the Muscle Mitochondrial Power Grid
NIH mouse study overturns scientific ideas on energy distribution in muscle.
Expanding the Brain
A team of researchers has identified more than 40 new “imprinted” genes, in which either the maternal or paternal copy of a gene is expressed while the other is silenced.
Identifying a Key Growth Factor in Cell Proliferation
Researchers discover that aspartate is a limiter of cell proliferation.
Study Uncovers Target for Preventing Huntington’s Disease
Scientists from Cardiff University believe that a treatment to prevent or delay the symptoms of Huntington’s disease could now be much closer, following a major breakthrough.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!