Navigation Links
New approach for growing bone comes from Duke preclinical research
Date:10/9/2009

DURHAM, N.C. The natural cycle of building bone to maintain skeletal strength and then breaking it down for the body's calcium needs is delicately balanced, but diseases like osteoporosis break down too much bone without adequate bone replacement, leading to bone fractures.

The results from a new study at Duke suggest a targeted approach by which drugs may be able to fight osteoporosis and other degenerative bone diseases. Diane Gesty-Palmer, M.D., a Duke Assistant Professor of Endocrinology and Metabolism, and her team have found a new mechanism of bone formation in mice that works without inducing the complementary bone breakdown. The work appears in the inaugural issue of Science Translational Medicine.

The science boils down to two biochemical pathways stemming from a cell surface receptor called G-protein coupled receptor (GPCR). This is the largest family of cell surface receptors and the target of numerous drugs for the treatment of many medical disorders. For many years, scientists thought the cellular actions of these receptors were solely controlled by activation of G-protein pathways.

But GPCR discoverer, Duke's Robert J. Lefkowitz, M.D., has also discovered that another molecule, beta-arrestin, works like a brake on G-protein activation. His lab has been learning about ways that beta-arrestin also can signal through different pathways and thus directly control certain cellular processes.

By combining their expertise in bone metabolism and GPCR signaling, Drs. Gesty-Palmer and Lefkowitz have found that beta-arrestin can cause bone to form, even though it blocks receptor activation of the G proteins. They discovered this happens in the receptor for parathyroid hormone (PTH), which regulates the amount of calcium in the body, and is used to treat osteoporosis.

By turning off G-protein signaling with a PTH analogue called PTH-Beta-arr (for beta-arrestin), the researchers were able to separate the bone-forming actions of the PTH receptor from its damaging bone-resorbing actions. They found much less bone was resorbed, and overall the amount of bone grew.

"We didn't anticipate finding bone growth because we thought that once the G-protein coupled pathway was blocked, that bone formation would also be blocked," Gesty-Palmer said. "It is commonly believed that the bone-forming actions of the parathyroid hormone receptor are mediated exclusively through G-protein activation."

"I think we will find that the beta-arrestin pathways play very important roles in the body," Lefkowitz said. "It is scientific convention that the G-protein dependent signaling pathways are the best pharmaceutical targets, but as we are learning more, we see that beta-arrestin dependent pathways also have an impact on physiological processes. Getting others to accept this, however, has been like turning around a battleship it happens very slowly."

"We keep refining the science," Lefkowitz said. "With this in vivo study, we have reached the next level of specificity. With what we have learned, we may begin to create the keys to unlock targeted groups of receptors with this higher level of specificity."

With this refinement, the researchers also may achieve the control needed to avoid certain drug side effects, Lefkowitz said. "We think the next generation of drugs, in this instance for osteoporosis, will behave more as we would like them to."

Dr. Lefkowitz has taken to calling the GPCRs, which he discovered, the 7-transmembrane receptors. This name reflects the characteristic structure of the receptor proteins which weave across the cell membrane seven times, and accommodates the fact that beta-arrestin pathways may also be activated by these receptors.


'/>"/>

Contact: Mary Jane Gore
mary.gore@duke.edu
919-660-1309
Duke University Medical Center
Source:Eurekalert

Related biology technology :

1. Global Regulators to Discuss Benefit-Risk Approaches of Medicinal Products at DIA Workshop
2. CELLECTA, INC. to Develop New Approach for Cancer Gene Discovery in Partnership with Roswell Park Cancer Institute and Health Research, Inc.
3. Synthesis and Purification of Peptide Libraries -- Innovative Approaches
4. Bio-enabled, surface-mediated approach produces nanoparticle composites
5. Clostridium difficile Infection: Strategic Approaches for Better Outcomes
6. DNA2.0 Awarded US Patents for Breakthrough Gene Optimization Technology -- Company's Unique Algorithm Enables Expression Yields up to 50 Times Greater than Competing Approaches
7. Roche Announces Back-to-Basics Approach to Diabetes Care - Simpler is Better
8. Amylin Pharmaceuticals Announces a New Sales Approach to Better Target the Diabetes Market
9. Collexis BiomedExperts Fast Approaching 150,000 Registered Users
10. Energy Leaders Gather in Houston; Call for Balanced, Careful Approach to Energy Policy
11. Prous Institute Presents Innovative Approach to Drug Discovery
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/29/2016)... ... , ... Intelligent Implant Systems announced today that the two-level components for the ... United States. These components expand the capabilities of the system and allow Revolution™ ... October of 2015, the company has seen significant sales growth in 1Q 2016, and ...
(Date:4/28/2016)... ... April 28, 2016 , ... ... will deliver a talk on its first-in-class technologies for tissue stem cell counting ... on RNAiMicroRNA Biology to Reprogramming & CRISPR-based Genome Engineering in Burlington, Massachusetts. ...
(Date:4/27/2016)... ... ... The Pittcon Organizing Committee is pleased to announce that Charles “Chuck” Gardner was named ... 1987. Since then, he has served in a number of key leadership positions including ... program and exposition committees. In his professional career, Dr. Gardner is the director of ...
(Date:4/27/2016)... ... 27, 2016 , ... NDA Partners Chairman Carl Peck, ... Expert Consultant. Mr. Clark was formerly a Vice President with US Pharmacopeia, ... molecule monographs based on analytical methods. NDA Partners Expert Consultants are top ...
Breaking Biology Technology:
(Date:4/13/2016)... 2016  IMPOWER physicians supporting Medicaid patients in ... clinical standard in telehealth thanks to a new partnership ... platform, IMPOWER patients can routinely track key health measurements, ... index, and, when they opt in, share them with ... a local retail location at no cost. By leveraging ...
(Date:3/31/2016)... , March 31, 2016  Genomics firm Nabsys ... founding CEO, Barrett Bready , M.D., who returned ... of the original technical leadership team, including Chief Technology ... of Product Development, Steve Nurnberg and Vice President of ... to the company. Dr. Bready served as ...
(Date:3/23/2016)... 23, 2016 ... Gesichts- und Stimmerkennung mit Passwörtern     ... MESG ), ein führender Anbieter digitaler ... mit SpeechPro zusammenarbeitet, um erstmals dessen Biometrietechnologie ... die Möglichkeit angeboten, im Rahmen mobiler Apps ...
Breaking Biology News(10 mins):