Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A direct path for understanding and treating brittle bones

23.05.2011
Study highlights roles of gene in load-sensing cells in bone growth; could guide research on treatments for bone diseases like osteoporosis

A study by researchers at Children's Hospital Boston and collaborators at other institutions has provided new insights into the means by which bone cells produce new bone in response to mechanical stresses, such as exercise. Their findings lay a path for developing new strategies for treating diseases characterized by low bone density, such as osteoporosis in adults and osteogenesis imperfecta in children.

The research team, led by Matthew Warman, MD, of the Orthopedic Research Laboratories (ORL) in the Department of Orthopedic Surgery at Children's Hospital Boston, published their findings on May 22 in the advanced online edition in Nature Medicine.

Warman, director of the ORL, and his colleagues developed mouse models to better understand the role of a gene called Lrp5 in bone growth. While the gene's exact functions remain unclear, Lrp5 is believed to help mature bone cells called osteocytes respond to changes in mechanical load and call for the production of more bone when needed. Mutations that turn Lrp5 off lead to brittle bones, while others that turn Lrp5 on too much, called high bone mass (HBM) mutations, cause bones to become extra strong.

Using a system that allowed the investigators to selectively express HBM mutations of Lrp5 in osteocytes, the team accurately recreated in the mice the increased bone strength seen in human patients with the same mutations, showing that Lrp5 functions locally in bone to regulate bone mass.

"These HBM mutations seem to fool the osteocytes, the most mature bone cells, into thinking they hadn't made enough bone tissue," said Warman, who is also a Howard Hughes Medical Institute investigator and a professor of genetics at Harvard Medical School. "This knowledge should bolster efforts to develop pharmacologic agents that function similarly to the HBM mutations, in order to trick bone cells into making more bone. In fact, several companies are pursuing these strategies, and our data provides strong support for their continuing this line of investigation."

The researchers also found that Lrp5's effects are quite localized. By turning HBM-Lrp5 on only in the bone cells of the limbs, and not of the spine, they found that bone density increased only in the limbs and not in the spine.

"These results tell us that Lrp5 is really working in mature bone cells," Warman said. "They also tell us that targeting mature bone cells might be enough to increase bone mass and treat diseases like osteoporosis and other skeletal fragility disorders."

In addition, the team found no connection between Lrp5, bone mass, and serotonin, a compound better known for its role as a neurotransmitter in the brain but which is also produced in the intestines. This disagrees with studies that had suggested that Lrp5 affects bone density indirectly through intestinal serotonin production, rather than directly within bone tissue itself.

"We wanted to independently confirm the previous publications which suggested that Lrp5 exerts its effect on bone via intestinal serotonin, but our data do not support this hypothesis," Warman noted. "While the notion that gut serotonin affects bone mass is intriguing, we hope that our results encourage other investigators to focus on examining the local role of Lrp5 in bone."

The findings also raise a number of new questions meriting further study. "We need to understand when we can influence Lrp5 in order to induce bone cells to build more bone. In our mice, the Lrp5 mutations causing increased bone mass were present at birth, whereas if we want to design therapies that could improve bone strength in adults with osteoporosis, who are in their 60's or 70's, we would need to study the effect of inducing the HBM mutations in aged mice, instead of newborn mice," Warman noted.

Warman continued, "We also need to better understand which genes and proteins function upstream and downstream in the Lrp5 signaling pathway. And we want to see whether strategies that target Lrp5 can help increase bone mass and improve bone strength in persons with inherited skeletal fragility conditions like osteogenesis imperfecta (OI). Even though using Lrp5 to increase bone formation will not fix the underlying genetic cause of a child's osteogenesis imperfecta, it may still be helpful in reducing the high rates of fracture that patients with OI commonly experience."

Warman went on to give high praise to the multi-institutional team from across academia and industry that worked on the study. "This was one of the best collaborative efforts that I've been privileged to be part of."

This study was supported by the Howard Hughes Medical Institute, the National Institutes of Health, the Leukemia and Lymphoma Society, and the Van Andel Research Institute.

Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including nine members of the National Academy of Sciences, 12 members of the Institute of Medicine and 13 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 395 bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about research and clinical innovation at Children's, visit: http://vectorblog.org.

Erin McColgan | EurekAlert!
Further information:
http://www.harvard.edu

Further reports about: Medical Wellness bone cells bone mass bone tissue mouse model orthopedic

More articles from Studies and Analyses:

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

New insights into the ancestors of all complex life

29.05.2017 | Earth Sciences

New photocatalyst speeds up the conversion of carbon dioxide into chemical resources

29.05.2017 | Life Sciences

NASA's SDO sees partial eclipse in space

29.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>