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 Spanish scientists create a 3-D bioprinter to print human skin
24.01.2017 | Carlos III University of Madrid

nachricht Tracking movement of immune cells identifies key first steps in inflammatory arthritis
23.01.2017 | Massachusetts General Hospital

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: Scientists spin artificial silk from whey protein

X-ray study throws light on key process for production

A Swedish-German team of researchers has cleared up a key process for the artificial production of silk. With the help of the intense X-rays from DESY's...

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Breaking the optical bandwidth record of stable pulsed lasers

24.01.2017 | Physics and Astronomy

Choreographing the microRNA-target dance

24.01.2017 | Life Sciences

Spanish scientists create a 3-D bioprinter to print human skin

24.01.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>