Discovery raises hopes for bone disease sufferers

Monash University researchers have identified two basic mechanisms that control the level of calcium deposition in bones and joints, a finding that could lead to treatments for osteoporosis and some forms of arthritis.

Professor James Goding and Mr Adnan Sali, in collaboration with researchers in San Diego, have discovered that the enzymes PC1 and alkaline phosphatase - which are found in bone and cartilage - are involved in controlling bone density.

The researchers are testing thousands of compounds to find potential drugs that interfere with these enzymes and which could be useful in treating some forms of arthritis. Improved understanding of the enzymes could also lead to better treatments for osteoporosis.

Initial research showed that high levels of the PC1 enzyme caused abnormal calcification of cartilage, leading to a condition similar to osteoarthritis. To find out more about the PC1 enzyme, the researchers studied mice in which the gene for the PC1 enzyme was removed.

The mice developed a kind of arthritis and, when X-rayed, were found to have abnormal calcium deposits in and around their joints, and their vertebrae were osteoporotic. "Our work showed that both over-production and under-production of PC1 led to faulty calcification," Prof. Goding said.

At about the same time, research in San Diego showed that mice that lacked the alkaline phosphatase gene for alkaline phosphatase lived only a week after birth and had severe abnormalities in their bones - a condition known as hypophosphatasia.

The groups then teamed up to study 'double knockout' mice in which both the PC1 and alkaline phosphatase genes were missing. The work showed that bone abnormalities caused by the lack of alkaline phosphatase could be counterbalanced by the removal of the PC1 gene and vice versa, and that normal bone development required a balance between the actions of these enzymes.

"The fact that knocking out PC1 partially corrects hypophosphatasia in mice means drugs that inhibit PC1 might help children with this disorder," Prof. Goding said.

Item provided courtesy of Monash University