RANKL in bone homeostasis

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Science  05 Oct 2018:
Vol. 362, Issue 6410, pp. 42-43
DOI: 10.1126/science.362.6410.42-a

Osteoporosis reduces bone density because of imbalances in signaling feedbacks.


Synthesis and breakdown of bone are tightly coupled to preserve skeletal function. Ikebuchi et al. show that signaling via a transmembrane receptor protein called receptor activator of nuclear factor–kappa B (RANK) and its ligand, RANKL, is involved in both processes. RANKL is released by bone-forming cells known as osteoblasts and stimulates RANK on the surface of stem cells to form osteoclasts, which are cells that mediate bone resorption. The same pair of proteins can also signal in reverse. In this case, RANK is released from osteoclasts in vesicles, and clusters of membrane-bound RANK activate signaling by RANKL molecules on the surface of osteoblasts to promote bone formation. Separating these two signals could prove beneficial to combat the excessive bone resorption that occurs during osteoporosis.

Nature 561, 195 (2018).

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