Coupling of bone resorption and formation by RANKL reverse signalling

Journal: Nature

Published: 2018-09-05

DOI: 10.1038/s41586-018-0482-7

Affiliations: 8

Authors: 13

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Research Highlight

Reverse signalling gives bone growth a boost

© QAI Publishing/Getty

© QAI Publishing/Getty

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.

Supported content

  1. Nature 561, 195–200 (2018). doi: 10.1038/s41586-018-0482-7
Institutions FC
Department of Pharmacy, UTokyo, Japan 0.23
The University of Tokyo Hospital, Japan 0.23
Department of Basic Oral Health Engineering, TMDU, Japan 0.23
Department of Pharmacology, TMDU, Japan 0.08
Institute of Molecular Biotechnology (IMBA), Austria 0.08
Department of Biochemistry, MDU, Japan 0.08
Department of Regeneration Science and Engineering, Kyoto University, Japan 0.04
Institute for Frontier Life and Medical Sciences (IFLMS), Kyoto University, Japan 0.04

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