Millions of people, especially for the aging people, are suffered by bone-loss diseases, such
as rheumatoid arthritis (RA) and osteoporosis. Therefore, better understanding the involved mechanisms
of bone metabolism is required for further treat on such diseases. Particularly, during the pathological
process of bone losing, RANKL as a member of the tumor necrosis factor (TNF) superfamily,
could induce osteoclast precursor cells differentiate into mature osteoclast, which grant its essential
role in osteolysis. In recent years, with the increased attention paid to the natural compounds discovering
studies, the therapeutic application of natural plant-derivatives have been widely recognized.
Therefore, our present study aim to summarize the current novel research progressions on RANKL
and its downstream signaling pathways in bone cellular differentiation, and provide a further insight
for RANKL as the important drug targets in bone loss diseases. Besides that, in our current study, we
also aim to briefly introduce the current application of several natural compounds for treating
RANKL-mediated osteoclastic activation by modulating the RANKL signaling pathway and their
therapeutic effects on the prevention of osteoporosis, osteoarthritis (OA) and RA.