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Protein could help treat bone and joint diseases

Half of all women over the age of 50 are expected to suffer at least one osteoporotic fracture. AAP/Robert McGrath

A protein with a bone-protective effect could help in the development of more powerful treatments for osteoporosis and other bone diseases, an international team of scientists has reported.

The protein, called semaphorin 3A (Sema3A), is expressed by cells that are responsible for bone formation. Mice treated with the protein showed improvements in their bone health, the team of researchers reported in the latest edition of Nature.

Osteoporosis affects almost 700,000 Australians, or more than 3% of the population. Women account for 82% of all cases, which occur mainly in people over the age of 55 years.

Hiroshi Takayanagi, from the Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, and the Centre for Orthopaedic Research at The University of Western Australia, said the discovery could “lead to better treatment developments for osteoporosis, arthritis or bone fractures. I also think Sema3A could be used as a bio-marker for disease diagnosis because we found that in the older mice where the amount of bone was dropping, the amount of Sema3A protein had also decreased.”

Professor Takayanagi and his team found that bone forming cells, or osteoblasts, produced Sema3A, which was previously known to regulate nerve and immune cells.

When used to treat mice, not only did Sema3A decrease bone breakdown but, unlike current osteoporosis medications, it also boosted bone formation.

“Osteoporosis treatments available today largely involve taking medication which suppresses bone resorption, but these drugs also suppress bone formation,” Professor Takayanagi said. “It has been hoped someone can develop a new drug which can control both bone resorption and formation to help recover the normal amount of bone.

"Our research team looked at Sema3A, a protein produced by osteoblasts which controls the development of neuron paths and inhibits T-cells in the body’s immune system. When we treated mice with Sema3A we found the protein was suppressing bone breakdown and speeding up bone formation at the same time.”

Gethin Thomas, Deputy Director of Education and Senior Research Fellow in the Muscoskeletal Genetics Group at The University of Queensland Diamantina Institute, said the burden of osteoporosis to the general community was “considerable”. Half of all women over the age of 50 were expected to suffer at least one osteoporotic fracture, Dr Thomas said.

“Most current approaches for osteoporosis therapy decrease the activity of osteoclasts to decrease bone degradation, but the gold standard is to find therapies that can build bone as well as stop bone degradation, as osteoporosis is frequently only diagnosed after the bones have already become very weak.

"This is a very exciting discovery identifying a completely new bone regulating pathway and one that is potentially very "druggable”. Indeed in this study they have shown that treating mice with Sema3A results in increased bone strength.“

But the pathway to a drug would provide many challenges, said T.J. Martin, Emeritus Professor of Medicine in the Bone Cell Biology and Disease Unit at St Vincent’s Institute of Medical Research and the University of Melbourne.

"The treatment studies in the paper are limited, but the control pathway revealed in the genetic experiments is of great interest, posing many further questions,” Professor Martin said. Although it is not easy to see Sema3A itself as a drug, it provides much that will influence thinking as attempts are made to develop the “holy grail” of an inhibitor of breakdown that promotes bone formation.“

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