Researchers find protein linked to osteoporosis(2011/10)

October 11th, 2011 | Categories: 2011 | Tags:

A National Cheng Kung University research team has discovered that a protein called interleukin (IL)-20 is key to treating osteoporosis, a disease that lowers a person’s bone density, researchers told a press conference in Taipei yesterday.

The discovery by the team led by Chang Ming-shi (張明熙), a professor at the Department of Biochemistry and Molecular Biology, was published in the Journal of Experimental Medicine and has drawn attention in academic circles and from the biotechnology industry.

The chief editor of Nature Reviews Rheumatology also commented on the finding in last month’s issue, while the Science-Business eXchange published a cover story reporting on the discovery in the same month.

IL-20 is a protein secreted by the immune system. When it is overproduced, it causes inflammation and destroys tissue, leading to chronic diseases.

There are two types of bone cells: osteoclasts and osteoblasts. Bone mineral density is determined by the balance between osteoclasts and osteoblasts. The relationship between IL-20 and osteoporosis has never been explored.

Chang’s team discovered that osteoporosis patients have higher than normal amounts of IL-20 in their blood, which suggests that IL-20 is involved in the progression of the disease. IL-20 increases the amount of two proteins important for bone metabolism — RANK on osteoclast precursors and RANKL on osteoblasts — and so stimulates osteoclast formation.

In a cell-based test, the team found that IL-20 antibodies completely inhibited the formation of osteoclasts from stem cells. They then created a mouse model of osteoporosis by removing their ovaries; these mice then showed symptoms of osteoporosis. However, an injection of IL-20 antibody into the mice protected them from osteoporosis and increased their bone mineral density.

The team also generated what are called gene-knock-out mice by permanently removing the IL-20 receptor (IL-20 R1) gene from the mice so that IL-20 was unable to attach to the bone cells. These mice had higher bone mineral density and were protected from osteoporosis even after their ovaries had been removed.

Chang’s team has provided evidence that IL-20 is a novel and undiscovered molecule involved in the formation of osteoclasts — a revolutionary discovery and a significant contribution to basic medicine.

The team has also showed that IL-20 is a novel target for osteoporosis and that the IL-20 antibody could be a potent new anti-osteoporosis drug with a significant effect on biotechnology.

The current anti-osteoporosis drug, denosumab, sold under the trade name Prolia, is an anti-RANKL antibody that was approved by the US Food and Drug Administration last year.

「IL-20 antibody not only blocks the production of IL-20, but also of the protein RANKL. Also, it affects not only osteoclast formation, but also osteoblast function,」 Chang said. 「If further developed into a therapeutic drug, IL-20 antibody should have many advantages over denosumab.」



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