Figure 2.

A schematic showing the relationship between RANK, RANKL, and OPG in activating or inhibiting osteoclastic activity and subsequent bone resorption. The binding of RANKL to the membrane-bound receptor RANK results in the activation of osteoclastic activity. However, OPG acts as a decoy and, if present, will bind to RANKL, thereby preventing RANK–RANKL interaction and osteoclastic activation. Thus, bone formation versus resorption is fundamentally dependent on the RANKL:OPG ratio, where increased RANKL expression results in bone resorption and increased OPG in bone formation. Many cells secrete either or both OPG or RANKL or both (e.g., osteocytes, osteoblasts, BMSCs, B-lymphocytes, and megakaryocytes). Regulation of the cellular response occurs via mechanical, hormonal, and growth factor-induced signaling, among others, making the overall governance of this system highly complex.