Hyperosmotic Stimulus Down-regulates 1α, 25-dihydroxyvitamin D3-induced Osteoclastogenesis by Suppressing the RANKL Expression in a Co-culture System

• Published in: The Korean journal of physiology & pharmacology 2010, 14(3), , pp.169-176
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Original; 약리학
• ISSN: 1226-4512; 2093-3827
• DOI: 10.4196/kjpp.2010.14.3.169

The hyperosmotic stimulus is regarded as a mechanical factor for bone remodeling. However, whether the hyperosmotic stimulus affects 1α, 25-dihydroxyvitamin D 3 (1α,25(OH) 2 D 3 )-induced osteoclastogenesis is not clear. In the present study, the effect of the hyperosmotic stimulus on 1α,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 1α,25(OH) 2 D 3 -induced tartrate-resistant acid phosphatase-positive multinucleated cells and 1α,25(OH) 2 D 3 -induced bone-resorbing pit area in a co-culture system. In osteoblastic cells, receptor activator of nuclear factor κB ligand (RANKL) and Runx2 expressions were down-regulated in response to 1α,25(OH) 2 D 3 . Knockdown of Runx2 inhibited 1α,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 1α,25(OH) 2 D 3 -induced osteoclastogenesis, suppressing Runx2 and RANKL expression due to the TonEBP overexpression in osteoblastic cells.