Study Links Psoriasis to Bone Loss. Is IL-17 to Blame?

Psoriasis is linked to widespread bone loss, according to Researchers from the Genes, Development and Disease Group at the Spanish National Cancer Research Centre (CNIO) in Madrid.

The new study, which appears in Science Translational Medicine, also describes the molecular communication that between the inflamed skin and loss of bone mass.

This discovery suggests that some psoriasis medications already on the market, or in advanced clinical trial stages, may have additional benefits for the bone.

“We have detected that psoriasis causes the widespread and progressive loss of bone tissue," explains researcher Özge Uluçkan, PhD, 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."

This occurs via a mechanism that inhibits the activity of the osteoblasts,

The Role of IL-17 and IL-17 Blockers

In a previous study, the same team generated a mouse model, from which they had removed the JunB gene in keratinocytes to mimick 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. 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, however, 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), they observed that psoriasis patients had bone loss when compared to healthy people, and this correlated with increased levels of IL-17A in blood.

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 Dr. 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 may 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 Dr. Uluçkan. "It would be interesting to study whether IL-17 is responsible for this secondary effect."

PHOTO CAPTION: 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