RANKL and RANK Biomarker Spotlight

Receptor activator of nuclear factor kappa B ligand, RANKL, and its specific receptor RANK, are members of the tumor necrosis factor (TNF) family and are the main stimulatory factor for the formation of mature osteoclasts and are essential for their survival. The major source of RANKL are osteocytes, former osteoblasts that become embedded within the mineralized bone matrix. RANKL and its specific receptor RANK are not only key regulators of bone remodeling but also play an essential role in immunobiology, e.g. lymph node formation, establishment of the thymic microenvironment, mammary gland development during pregnancy, bone metastasis in cancer and sex-hormone, progestin-driven breast cancer, thermoregulation, and finally in the development of type 2 diabetes mellitus.

A recent study has uncovered a new role for RANKL and RANK in bone remodeling. Researchers have found that extracellular vesicles containing RANKL and RANK may have an important role in the long range signaling for bone remodeling. These signaling molecules have the potential to be targeted for therapeutics and also used diagnostically.

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Holliday LS, Patel SS, Rody WJ. RANKL and RANK in Extracellular Vesicles: Surprising New Players in Bone Remodeling. Extracell Vesicles Circ Nucleic Acids. 2021; 2:18-28.

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