• Title/Summary/Keyword: Hyperosmotic stimulus

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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;Jeong, Hyun-Joo;Lee, Sang-Do;Kong, Seok-Heui;Ohk, Seung-Ho;Yoo, Yun-Jung;Seo, Jeong-Taeg;Shin, Dong-Min;Sohn, Byung-Wha;Lee, Syng-Ill
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.3
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    • pp.169-176
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    • 2010
  • 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.