The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Hyperosmotic Stimulus Down-regulates $1{\alpha}$, 25-dihydroxyvitamin $D_3$-induced Osteoclastogenesis by Suppressing the RANKL Expression in a Co-culture System

  • Tian, Yu-Shun (Department of Oral Biology, Yonsei University) ;
  • Jeong, Hyun-Joo (Department of Oral Biology, Yonsei University) ;
  • Lee, Sang-Do (Department of Physiology, College of Medicine, Chungnam National University) ;
  • Kong, Seok-Heui (Department of Orthodontics, Yonsei University) ;
  • Ohk, Seung-Ho (Department of Oral Microbiology, College of Dentistry, Chonnam National University) ;
  • Yoo, Yun-Jung (Department of Oral Biology, Yonsei University) ;
  • Seo, Jeong-Taeg (Department of Oral Biology, Yonsei University) ;
  • Shin, Dong-Min (Department of Oral Biology, Yonsei University) ;
  • Sohn, Byung-Wha (Department of Orthodontics, Yonsei University) ;
  • Lee, Syng-Ill (Department of Oral Biology, Yonsei University)
  • Received : 2010.05.12
  • Accepted : 2010.06.07
  • Published : 2010.06.30
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Abstract

The hyperosmotic stimulus is regarded as a mechanical factor for bone remodeling. However, whether the hyperosmotic stimulus affects $1{\alpha}$, 25-dihydroxyvitamin $D_3$ ($1{\alpha},25(OH)_2D_3$)-induced osteoclastogenesis is not clear. In the present study, the effect of the hyperosmotic stimulus on $1{\alpha},25(OH)_2D_3$-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 $1{\alpha},25(OH)_2D_3$-induced tartrate-resistant acid phosphatase-positive multinucleated cells and $1{\alpha},25(OH)_2D_3$-induced bone-resorbing pit area in a co-culture system. In osteoblastic cells, receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL) and Runx2 expressions were down-regulated in response to $1{\alpha},25(OH)_2D_3$. Knockdown of Runx2 inhibited $1{\alpha},25(OH)_2D_3$-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 $1{\alpha},25(OH)_2D_3$-induced osteoclastogenesis, suppressing Runx2 and RANKL expression due to the TonEBP overexpression in osteoblastic cells.

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References

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