Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New hints into development of osteoporosis

05.03.2003


Defects in a protein called alphaV beta3 ntegrin appear to contribute to the development of osteoporosis, and these effects can be reversed by enhancing a protein called macrophage-colony-stimulating factor (M-CSF), according to research at Washington University School of Medicine in St. Louis.



The study appears in the first March issue of the Journal of Clinical Investigation and is published online March 4.

"Because of our previous research with these proteins, new drugs already are in clinical trials," says lead investigator Steven L. Teitelbaum, M.D., the Wilma and Roswell Messing Professor of Pathology and Immunology. "But we still do not understand how these proteins interact to affect bone-cell development. This study brings us significantly closer to determining that mechanism."


Osteoporosis, a condition that results in weakened, brittle bones, afflicts roughly 50 percent of Caucasian and Asian women after age 65. It develops when bone is broken down at a faster rate than it is synthesized. Therefore, curing the disease and others like it depends on understanding osteoclasts -- cells responsible for eroding bone -- and determining why they sometimes become overly active.

Teitelbaum’s team previously determined that M-CSF helps unspecialized bone cells develop into mature osteoclasts. Without enough M-CSF to encourage osteoclast growth, animals develop abnormally dense bone. Similarly, it is known that blocking alphaV beta3 integrin in animal models causes failure of osteoclast function. However, it is unclear precisely how M-CSF or alphaV beta3 integrin influence osteoclast development.

The absence of beta 3 (part of the alphaV beta3 integrin) in precursor cells has a curiously different effect on cells in a petri dish compared with cells in living animals. When grown in a dish, abnormally few osteoclasts develop, and those that do develop are dysfunctional. In animals, however, precursor cells lacking beta3 produce abnormally high numbers of osteoclasts.

"This paradox suggests that something in the living animal interacts with beta3 during the process of osteoclast differentiation," Teitelbaum explains.

His team discovered the interaction may involve M-CSF. When they took precursor cells from mice lacking beta3 and put them in a petri dish very few became osteoclasts. But when levels of M-CSF were increased, the stunted growth effect was reversed. Furthermore, they determined that a particular structure on the surface of the cell (c-Fms tyrosine 697, a component of the protein designed to bind to M-CSF) appears to be largely responsible for this interaction.

"The interaction between M-CSF and alphaV beta3 integrin is intriguing and may help explain some of the less-understood aspects of animal models of osteoporosis," Teitelbaum says.

Because of this interaction, Teitelbaum and colleagues also explored whether alphaV beta3 integrin and M-CSF are involved in the same signaling pathway that causes precursor cells to differentiate into osteoclasts. They found increased levels of M-CSF also restored activity of externally regulated kinases (ERKs) and a protein called c-Fos, which are critical for stimulating the cascade of events that lead to bone-cell differentiation. Since alphaV beta3 integrin also is known to contribute to the activation of ERKs and c-Fos, the team concludes that the alphaV beta3 integrin and M-CSF collaborate in the process of osteoclast differentiation.



Faccio R, Takeshita S, Zallone A, Ross FP, Teitelbaum SL. c-Fms and the avb3 integrin collaborate during osteoclast differentiation. Journal of Clinical Investigation, March 2003.

Funding from the National Institutes of Health, Pharmacia Corp, the Italian Foundation for Cancer Research and the Italian Space Agency supported this research.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Gila Z. Reckess | EurekAlert!
Further information:
http://medinfo.wustl.edu/

More articles from Health and Medicine:

nachricht A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital

nachricht Stem cell transplants: activating signal paths may protect from graft-versus-host disease
20.04.2017 | Technische Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

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...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

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...

Im Focus: Deep inside Galaxy M87

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...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

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...

Im Focus: Microprocessors based on a layer of just three atoms

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Fraunhofer HHI with latest VR technologies at NAB in Las Vegas

24.04.2017 | Trade Fair News

New quantum liquid crystals may play role in future of computers

21.04.2017 | Physics and Astronomy

A promising target for kidney fibrosis

21.04.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>