ESPE Abstracts (2019) 92 PL1

RANKL and RANK: Bone and Beyond

Josef Penninger

University of British Columbia, Vancouver, Canada

RANKL was identified as an osteoclast differentiation factor as well as a T cell-derived stimulator of dendritic cells. The essential role of RANKL in osteoclastogenesis has been genetically proven in both mice and humans. In addition, RANKL was shown to play a critical role in various tissues including the thymus, gut, and mammary gland. The fully human monoclonal antibody against RANKL, denosumab, has been successfully utilized and approved for the treatment of bone metastasis and osteoporosis. We also studied the mechanism of bone destruction in rheumatoid arthritis and proposed that RANKL is a key therapeutic target for arthritis-associated bone destruction. Recently, denosumab has been indeed approved for rheumatoid arthritis in Japan. I will discuss the function of RANKL in multiple tissues and introduce recent findings providign an evolutionary perspective of RANKL/RANK signaling.

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