Coupling of bone resorption and formation by RANKL reverse signalling
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A well-known bone-removal pathway can operate in reverse to stimulate bone production, a Japan-led team has discovered. This finding could lead to new therapies for osteoporosis and other skeletal disorders.
A group that included scientists from Tokyo Medical and Dental University showed that bone-resorbing cells secrete a kind of membrane-bound packet, called a vesicle, with the RANK receptor on its surface. RANK’s binding partner, RANKL, is normally discharged from bone-forming cells, but the researchers showed that it can also stay on the cell surface, where it binds RANK-bearing vesicles to promote bone formation.
The researchers developed an antibody drug that, because of its dual mechanism of action, could prove more efficacious than other anti-RANKL agents on the market. The novel RANKL-targeted antibody not only inhibited bone resorption, as other drugs do, it also promoted bone growth by activating bone-forming cells with RANKL displayed on their surface.
- Nature 561, 195–200 (2018). doi: 10.1038/s41586-018-0482-7
|Tokyo Medical and Dental University (TMDU), Japan||0.31|
|The University of Tokyo (UTokyo), Japan||0.23|
|The University of Tokyo Hospital, Japan||0.23|
|Kyoto University, Japan||0.08|
|Institute of Molecular Biotechnology (IMBA), Austria||0.08|
|Matsumoto Dental University (MDU), Japan||0.08|