title: Hyperosmotic Stimulus Down-regulates 1alpha, 25-dihydroxyvitamin D(3)-induced Osteoclastogenesis by Suppressing the RANKL Expression in a Co-culture System.
abstract: 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.
authors.affiliation: Department of Oral Biology, Yonsei University, Seoul 120-752, Korea.
authors.forename: Yu Shun
authors.initials: YS
authors.lastname: Tian
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Sang-Do
authors.initials: SD
authors.lastname: Lee
authors.forename: Seok Heui
authors.initials: SH
authors.lastname: Kong
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Ohk
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Yoo
authors.forename: Jeong-Taeg
authors.initials: JT
authors.lastname: Seo
authors.forename: Dong Min
authors.initials: DM
authors.lastname: Shin
authors.forename: Byung-Wha
authors.initials: BW
authors.lastname: Sohn
authors.forename: Syng-Ill
authors.initials: SI
authors.lastname: Lee