[Regulation of bone resorption by osteocytes]

Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Using a newly established method for the isolation of high purity osteocytes from bone matrix, we showed that osteocytes express a much higher amount of RANKL and have a much greater capacity to support osteoclastogenesis than osteoblasts and bone marrow stromal cells. The crucial role of RANKL expressed by osteocytes was validated by the severe osteopetrotic phenotype observed in mice lacking RANKL specifically in osteocytes. Thus, osteocytes are the commander cell at the initiation of the bone remodeling through regulation of osteoclastogenesis.