Hyperosmotic Stimulus Down-regulates 1Ձ, 25-dihydroxyvitamin D<SUB>3</SUB>- induced Osteoclastogenesis by Suppressing the RANKL Expression in a Co-culture System
Hyperosmotic Stimulus Down-regulates 1Ձ, 25-dihydroxyvitamin D<SUB>3</SUB>- induced Osteoclastogenesis by Suppressing the RANKL Expression in a Co-culture System
- Yu Shun Tian Hyun Joo Jeong Sang-Do Lee Seok Heui Kong Seung-Ho Ohk Yun-Jung Yoo Jeong-Taeg Seo Dong
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제14권 제3호
- 등재여부 : KCI등재
- 2010.01
- 169 - 176 (8 pages)
The hyperosmotic stimulus is regarded as a mechanical factor for bone remodeling. However, whether the hyperosmotic stimulus affects 1Ձ, 25-dihydroxyvitamin D<sub>3</sub> (1Ձ,25(OH)<sub>2</sub>D<sub>3</sub>)-induced osteoclastogenesis is not clear. In the present study, the effect of the hyperosmotic stimulus on 1Ձ,25(OH)<sub>2</sub>D<sub>3</sub>- 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 1Ձ,25(OH)<sub>2</sub>D<sub>3</sub>-induced tartrate-resistant acid phosphatase-positive multinucleated cells and 1Ձ,25(OH)<sub>2</sub>D<sub>3</sub>-induced bone-resorbing pit area in a co-culture system. In osteoblastic cells, receptor activator of nuclear factor ՊB ligand (RANKL) and Runx2 expressions were down-regulated in response to 1Ձ,25(OH)<sub>2</sub>D<sub>3</sub>. Knockdown of Runx2 inhibited 1Ձ,25(OH)<sub>2</sub>D<sub>3</sub>-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 1Ձ,25(OH)<sub>2</sub>D<sub>3</sub>- induced osteoclastogenesis, suppressing Runx2 and RANKL expression due to the TonEBP overexpression in osteoblastic cells.