Bone loss research team discovers how acid interacts with osteoclasts

London, ON – Researchers at the Canadian Institutes of Health Research (CIHR) group in skeletal development and remodeling at Western say they have discovered how the acid in the body interacts with the cells responsible for bone loss and what can be done to stop it.

“The discovery helps us understand the biological basis of several diseases affecting bone, such as rheumatoid arthritis and the spread of cancer within the skeleton,” says Jeff Dixon, director of the CIHR group in skeletal development and remodeling and professor of physiology & pharmacology and dentistry at Western. “More importantly, this discovery may lead to the development of drugs that reduce bone loss, without disrupting the rebuilding of normal bone.”

Physicians and researchers have known for the last 100 years that too much acid in the body (known as acidosis) causes bone loss. Acidosis can result from illnesses like kidney disease, diabetes, and chronic lung disease, leading to further medical complications such as osteoporosis.

To provide answers to how the acid leads to bone loss, the research team examined the role of a protein called NFAT in mediating the effects of acidosis on osteoclasts, the cells responsible for bone destruction. They found that acidosis triggers a receptor called OGR1 on osteoclasts. This leads to an increase of cytosolic calcium, which activates NFAT leading to bone loss. These findings suggest that new drugs targeted at the OGR1 receptor could stop the bone loss that results from acidosis.

The findings were published in the recent edition of Proceedings of the National Academy of Sciences. The study was funded through a partnership of CIHR, IMHA and the Arthritis Society, and by the Canadian Arthritis Network-a member of the federal Networks of Centres of Excellence, Canada’s flagship science and technology program.

The research team includes postdoctoral fellows Dr Svetlana V Komarova and Dr Alexey Pereverzev, undergraduate dental student Jonathan Shum, and Dr Stephen Sims, a researcher in the CIHR group in skeletal development and remodeling and professor of physiology & pharmacology.