Osteoblasts Suppress Bone Resorption Via Production of Osteoprotegerin

Osteoprotegerin (OPG) inhibits the ability of receptor activator of NFkB ligand (RANKL) to stimulate the differentiation, activity, and survival of bone resorbing osteoclasts. Genetic studies in mice show that osteocytes are an important source of RANKL, but the cellular sources of OPG are unclear. We used conditional deletion of Tnfrsf11b, which encodes OPG, from different cell populations to identify functionally relevant sources of OPG in mice. Deletion from B lymphocytes and osteocytes, two cell types commonly thought to supply OPG, had little or no impact on bone mass. In contrast, deletion of Tnfrsf11b from osteoblasts increased bone resorption and reduced bone mass to an extent similar to germline deletion, demonstrating that osteoblasts are an essential source of OPG. These results suggest that, in addition to producing new bone matrix, osteoblasts also play an active role in terminating the resorption phase of the bone remodeling cycle by suppressing RANKL activity.