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Inhibition of 1α,25(OH)2D3 induced osteoclastogenesis by hypertonic volume change of mouse osteoblastic cells

Other Titles
 조골세포 용적변화에 의한 1α,25(OH)2D3 induced osteoclastogenesis의 억제효과. 
Authors
 김보혜 
Issue Date
2002
Description
Dept. of Dentistry/박사
Abstract
[한글]



조골세포 용적변화가 1α,25(OH)₂D₃에 의한 파골세포의 분화과정 (osteoclastogenesis)에 미치는 영향을 규명하기 위하여 이 연구를 시행하였다. 조골세포와 파골세포 전구세포를 함께 배양하는 혼합배양법을 이용하였으며, sucrose를 첨가하여 조골세포의 용적변화를 유도하였다. Sucrose 첨가시 농도에 비례하여 1α,25(OH)₂D₃에 의한 파골세포 분화가 억제되었으며, 이러한 억제효과는 mannitol 과 NaCl을 첨가하여도 같은 결과를 보였다. 또한, 50 mM sucrose 첨가시 조골세포 용적이 약 35% 감소하였으며, 이러한 조골세포 용적 변화가 어떤 과정을 통하여 파골세포 분화를 억제하는지 밝히기 위하여, RT-PCR 기법을 이용하여 조골세포에서 RANKL, OPG, 그리고 M-CSF mRNA 발현을 측정하였다. Hypertonic stress 결과 조골세포의 용적감소로 RANKL mRNA의 발현이 감소된 반면에, OPG와 M-CSF mRNA 발현의 변화는 없었다. 더욱이 시간에 따른 RANKL mRNA 발현 양상을 검토한 결과, 48시간까지는 감소하였으나 72시간 이후에는 다시 회복되었다. 결론적으로 조골세포의 용적감소가 파골세포 분화를 차단하는 조절인자중 하나라고 생각되며, 특히 파골세포 분화초기 RANKL mRNA 발현의 down- regulation이 성숙된 파골세포수를 결정하는 중요한 요인으로 판단된다.





[영문]

To investigate the physiological role of volume change of osteoblasts, hypertonic shrinkage was applied to osteoblasts or osteoblast/bone marrow coculture by the addition of sucrose. The treatment of sucrose to osteoblast/bone marrow coculture inhibited the osteoclast differentiation induced by 10 nM 1α,25(OH)₂D₃. The inhibitory effect of cellular shrinkage on the osteoclast differentiation was confirmed by cellular shrinkage adding of mannitol or NaCl. Hypertonic shrinkage induced by not only sucrose but also mannitol or NaCl inhibited the osteoclast differentiation. When 50 mM sucrose was added to osteoblasts, 35% of the average cellular volume was reduced. For further study, the alterations of signal molecules at the cellular level by cell volume change were examined. Hypertonic challenges (addition of 50 mM sucrose) were applied directly to osteoblast and expression of RANKL, OPG, and M-CSF mRNA which concerns with osteoclastogenesis were monitored. As a results, hypertonic shrinkage of osteoblast caused the reduction of RANKL

mRNA expression. Such a decrease was dependent on the concentration of sucrose in the medium which osteoblasts were exposed. On the other hand, time dependent manners of sucrose on the RANKL mRNA expression were also observed. The RANKL mRNA

expression was blunted up to 48 hours in the period of hypertonic stress by the addition of 50 mM sucrose. However such a decrement was recovered after 72 hours of hypertonic stress. While, there was no any other changes in the OPG and M-CSF mRNA expression. Conclusively, these findings strongly suggest that hypertonic shrinkage of osteoblasts may be speculated as one of the regulators which modulate the cellular signal transduction on osteoclastogenesis. In especial, the down-regulation of RANKL mRNA expression at the initial period of osteoclast differentiation might be crucial event to determine the number of the matured osteoclasts.
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Appears in Collections:
2. College of Dentistry (치과대학) > Others (기타) > 3. Dissertation
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/127823
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