Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

CNIO scientists discover a link between psoriasis and general bone loss

17.03.2016

Researchers from the Genes, Development and Disease Group, headed by Erwin Wagner at the Spanish National Cancer Research Centre (CNIO) have discovered that psoriasis patients experience a widespread bone loss as a result of the disease. In addition, this paper, which is being published in the journal Science Translational Medicine, describes the molecular communication that is established between the inflamed skin and loss of bone mass. This discovery highlights the possibility to treat psoriasis with drugs that are already on the market, or in advanced clinical trial stages, that would have additional benefits for the bone.

Psoriasis is a chronic autoimmune disorder that affects 2% of the world population and more than one million people in Spain. It is characterised by inflammation and scaling of the skin, accompanied by a greater risk of contracting some type of metabolic syndrome, predisposing patients to pathologies, such as obesity, diabetes or cardiovascular diseases. Now, CNIO researchers have discovered a new feature of this inflammatory disorder.


Left, shows a histological image of healthy mouse bone. Right, shows bone from which the JunB gene of the epidermis has been deleted and where the loss of bone tissue can be seen.

Credit: CNIO

"We have detected that psoriasis causes the widespread and progressive loss of bone tissue," explains the researcher Özge Uluçkan, first author of the study. "There is no active destruction of the bone; on the contrary, during the bone regeneration cycle, bone is not formed at the necessary speed to replace what is being lost and, therefore, patients' bone mass reduces over time."

The process takes place by means of a mechanism --unveiled in this study -- that inhibits the activity of the osteoblasts, the cells that produce the bone matrix so that bones can grow during childhood and youth, and remain in good condition in adulthood.

IL-17, A CHANNEL OF COMMUNICATION BETWEEN THE SKIN AND BONE

In a previous study (Meixner et al, Nat Cell Biol, 2008), Erwin Wagner's team generated a mouse model, from which they had removed the JunB gene in keratinocytes -- cells that form the epidermis -- mimicking what happens during cutaneous inflammatory disorders in humans. Now, they have observed that this mouse mutant suffers from bone loss.

The researchers found that the immune cells in the skin of this animal model generated large amounts of the cytokine IL-17 -- a protein of the immune system that activates cellular inflammation in response to damage. IL-17 travels through the bloodstream to the bones. Once there, the protein acts on the osteoblasts and inhibits Wnt activity, which is a cellular signalling pathway that is involved in the formation of the skeleton and in certain disorders, such as osteoporosis, arthritis and myeloma. Treating these mice with IL-17 blockers allows the Wnt pathway to regain its normal activity and leads to bone formation.

A second mouse model, induced by overexpression of IL-17 in skin, also shows bone loss, and suggests that the deregulation of the protein is sufficient to cause this effect.

Subsequently, they analyzed a hundred human samples. Using high resolution peripheral computed tomography (XtremeCT) -- an imaging method known as virtual bone biopsy -- they observed that psoriasis patients had bone loss when compared to healthy people, and this correlated with increased levels of cytokine IL-17A in blood.

TREATMENT AND IMPLICATIONS FOR OTHER DISEASES

These observations suggest that patients with psoriasis should be monitored for this loss of bone mass, or the presence of high levels of these factors in the blood.

"Treating psoriasis patients with IL-17 blockers -- some already on the market -- could have a beneficial effect on the loss of bone tissue, unlike other compounds that might only affect skin inflammation," says Uluçkan. Antibodies that act on the Wnt signalling pathway are also being developed as a therapy for osteoporosis that could prove useful in these cases.

The findings of this study could also have implications for other autoimmune disorders. "IL-17 has become a focus point for the investigation of the immune system. Its deregulation is not only related to psoriasis, but also to other diseases, such as rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis. Some of these have been linked to loss of bone tissue, as in the case of inflammatory bowel disease, found in 70% of cases," explains Uluçkan. "It would be interesting to study whether IL-17 is responsible for this secondary effect."

###

This work has been carried out in collaboration with the Universities of Mainz, Hamburg and Erlangen-Nuremberg in Germany, and the CNIO Bioinformatics Unit. Erwin Wagner was funded by the Spanish Ministry of Economy and Competitiveness, the BBVA Foundation, and the European Research Council (ERC), and Özge Uluçkan by EMBO, Spanish Ministry of Economy and Competitiveness, and ECTS-AMGEN.

Reference article:

Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts. Özge Uluçkan, Maria Jimenez, Susanne Karbach, Anke Jeschke, Osvaldo Graña, Johannes Keller, Björn Busse, Andrew L. Croxford, Stephanie Finzel, Marije Koenders, Wim Van Den Berg, Thorsten Schinke, Michael Amling, Ari Waisman, Georg Schett, Erwin F. Wagner. Science Translational Medicine (2016). doi: 10.1126/scitranslmed.aad8996

Nuria Noriega | EurekAlert!

More articles from Health and Medicine:

nachricht Natural metabolite can suppress inflammation
01.07.2016 | ITMO University

nachricht Benign bacteria block mosquitoes from transmitting Zika, chikungunya viruses
01.07.2016 | University of Wisconsin-Madison

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: Mainz-based physicists find missing link between glass formation and crystallization

Densified regions with drastically reduced internal motion either act as crystal precursors or cluster and frustrate all further dynamics

Glasses are neither fluids nor crystals. They are amorphous solids and one of the big puzzles in condensed matter physics. For decades, the question of how...

Im Focus: Thousands on one chip: New Method to study Proteins

Since the completion of the human genome an important goal has been to elucidate the function of the now known proteins: a new molecular method enables the investigation of the function for thousands of proteins in parallel. Applying this new method, an international team of researchers with leading participation of the Technical University of Munich (TUM) was able to identify hundreds of previously unknown interactions among proteins.

The human genome and those of most common crops have been decoded for many years. Soon it will be possible to sequence your personal genome for less than 1000...

Im Focus: Optical lenses, hardly larger than a human hair

3D printing enables the smalles complex micro-objectives

3D printing revolutionized the manufacturing of complex shapes in the last few years. Using additive depositing of materials, where individual dots or lines...

Im Focus: Flexible OLED applications arrive

R2D2, a joint project to analyze and development high-TRL processes and technologies for manufacture of flexible organic light-emitting diodes (OLEDs) funded by the German Federal Ministry of Education and Research (BMBF) has been successfully completed.

In contrast to point light sources like LEDs made of inorganic semiconductor crystals, organic light-emitting diodes (OLEDs) are light-emitting surfaces. Their...

Im Focus: Unexpected flexibility found in odorant molecules

High resolution rotational spectroscopy reveals an unprecedented number of conformations of an odorant molecule – a new world record!

In a recent publication in the journal Physical Chemistry Chemical Physics, researchers from the Max Planck Institute for the Structure and Dynamics of Matter...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Quantum technologies to revolutionise 21st century - Nobel Laureates discuss at Lindau

30.06.2016 | Event News

International Conference ‘GEO BON’ Wants to Close Knowledge Gaps in Global Biodiversity

28.06.2016 | Event News

ERES 2016: The largest conference in the European real estate industry

09.06.2016 | Event News

 
Latest News

Mainz-based physicists find missing link between glass formation and crystallization

01.07.2016 | Physics and Astronomy

Scientists observe first signs of healing in the Antarctic ozone layer

01.07.2016 | Earth Sciences

MRI technique induces strong, enduring visual association

01.07.2016 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>