Searchable abstracts of presentations at key conferences on calcified tissues
Bone Abstracts (2013) 1 PP240 | DOI: 10.1530/boneabs.1.PP240

Department of Pharmacy, The University of Tokyo Hospital, Tokyo, Japan.


RANKL is the central player in the regulation of osteoclastogenesis and the quantity of RANKL presented to osteoclast precursors is an important factor determining the magnitude of osteoclast formation. It had been believed for years that osteoblastic cells are the major source of RANKL presented to osteoclast precursors, and we have previously focused on RANKL intracellular behavior in osteoblastic cells. However, recent two reports controverted this traditional concept and showed that the osteocyte is a central player in regulating physiological osteoclastogenesis. Hence, we faced the urgent need to reinvestigate the molecular mechanisms involved in the regulation of osteoclast formation by osteocytes. Osteocytes are derived from osteoblasts encased in bone matrix during the process of bone formation and undergo changes in cell shape and ultrastructure. Osteocyte dendritic processes are known to be lost when osteocytes are isolated from bone matrix and placed in conventional 2D culture conditions, making the study of osteocyte functions in vitro difficult. In the present study, we developed a novel co-culture system of osteoclast precursors and osteocytes embedded in collagen gel to analyze how osteocytes support osteoclastogenesis. Experiments using this model revealed that osteocytic RANKL is provided as a membrane-bound form to osteoclast precursors through osteocyte dendritic processes and that the contribution of soluble RANKL to the osteoclastogenesis supported by osteocytes is minor. Moreover, the regulation of RANKL subcellular trafficking, such as OPG-mediated transport of newly synthesized RANKL molecules to lysosomal storage compartments, and the release of RANKL to the cell surface upon stimulation with RANK, are confirmed to be functional in osteocytes. These results provide a novel understanding of the regulation of osteoclastogenesis.

Volume 1

European Calcified Tissue Society Congress 2013

Lisbon, Portugal
18 May 2013 - 22 May 2013

European Calcified Tissue Society 

Browse other volumes

Article tools

My recent searches

No recent searches.

My recently viewed abstracts