Hyperosmotic Stimulus Down-regulates 1alpha, 25-dihydroxyvitamin D(3)-induced Osteoclastogenesis by Suppressing the RANKL Expression in a Co-culture System.
The hyperosmotic stimulus is regarded as a mechanical factor for bone remodeling. However, whether the hyperosmotic stimulus affects 1alpha, 25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3))-induced osteoclastogenesis is not clear. In the present study, the effect of the hyperosmotic stimulus on 1alpha,25(OH)(2)D(3)-induced osteoclastogenesis was investigated in an osteoblast-preosteoclast co-culture system. Serial doses of sucrose were applied as a mechanical force. These hyperosmotic stimuli significantly evoked a reduced number of 1alpha,25(OH)(2)D(3)-induced tartrate-resistant acid phosphatase-positive multinucleated cells and 1alpha,25(OH)(2)D(3)-induced bone-resorbing pit area in a co-culture system. In osteoblastic cells, receptor activator of nuclear factor kappaB ligand (RANKL) and Runx2 expressions were down-regulated in response to 1alpha,25(OH)(2)D(3). Knockdown of Runx2 inhibited 1alpha,25(OH)(2)D(3)-induced RANKL expression in osteoblastic cells. Finally, the hyperosmotic stimulus induced the overexpression of TonEBP in osteoblastic cells. These results suggest that hyperosmolarity leads to the down-regulation of 1alpha,25(OH)(2)D(3)-induced osteoclastogenesis, suppressing Runx2 and RANKL expression due to the TonEBP overexpression in osteoblastic cells.
Tian
Yu Shun
YS
Department of Oral Biology, Yonsei University, Seoul 120-752, Korea.
Jeong
Hyun Joo
HJ
Lee
Sang-Do
SD
Kong
Seok Heui
SH
Ohk
Seung-Ho
SH
Yoo
Yun-Jung
YJ
Seo
Jeong-Taeg
JT
Shin
Dong Min
DM
Sohn
Byung-Wha
BW
Lee
Syng-Ill
SI