Inhibiting a Protein Prevents Bone Loss

The scientists involved in the study created a drug they called RRI (short for RANK receptor inhibitor), which interferes with the action of the mouse protein RANK. The latter is closely associated with the maturation and action of osteoclasts, the cells that engage in bone destruction, a normal process that constantly occurs in the body but can get out of hand to produce a variety of bone-loss disorders.

RANK is essential for many other bodily processes, such as immune-system function and breast development, so it’s not apparent that something that inhibits it would be at all useful, because of the inhibitor’s potentially many and harmful side effects. However, the Korean researchers found a particular part of the RANK molecule that’s specific for osteoclast formation, and targeted RRI to that area.
   
In laboratory dishes, RRI was found to inhibit the formation of mouse osteoclasts and to hinder bone destruction by osteoclasts. Yet more important, it prevented bone loss in two mouse models of diseases associated with bone destruction, suggesting that similar drugs might help people with disorders involving abnormal bone loss, such as osteoporosis.
   
“Although these molecules are attractive targets for therapeutic intervention in bone diseases,” the authors said, “they are also involved in normal cellular physiology, such as mounting effective immune and other cellular responses. In this regard, unraveling RANK signaling pathways, as was done in this study, will be beneficial for the development of new generations of therapeutics with high efficacy and fewer side effects."