By controlling the expresssion of the gene for the NFATc1 protein, scientists have been able to induce bone accummulation. They say this could be a potential drug target to treat or prevent bone degradation, osteoporosis and bone fractures. This fortuitous discovery resulted from observations showing that cyclosporine --an immunosuppresant drug used to treat arthritis and psoriasis and to prevent organ transplant rejection-- resulted to a decrease in bone mass. Cyclosporin does this by inhibiting a signaling protein complex known as calcineurin, which, in turn, chemically modifies the NFATc family of proteins. Since suppression of the calcineurin/NFATc activity resulted to bone loss, then activating these regulatory switches should result to increased bone mass. Tests in mice indeed showed positive results.

The researchers found that mice with enhanced NFATc activity in their osteoblasts had many more of these bone-forming cells, which explained the increase in bone mass. They also found a possible explanation for why there were more bone-destroying osteoclasts. Osteoblasts with hyperactive NFATc expressed higher levels of inflammatory proteins called chemokines, which promote osteoclast development.

According to the researchers, this findings holds a lot of promise in treating osteoporosis.

Very little NFATc1 must be activated to build extra bone, Winslow noted, which means that it may be possible to up-regulate the calcineurin/NFATc pathway to promote bone formation without disturbing other organ systems that use this same pathway.

They are now screening chemical libraries that could perform the task. Read more from the Howard Hughes Medical Institute News: A New Way to Build Bone.

[Photo: Medline Plus]