BIOLOGICAL CONTROL OF OSTEOCLASTS AND OSTEOBLASTS
Grant-in-Aid for Scientific Research (A)
|Allocation Type||Single-year Grants|
|Research Institution||THE UNIVERSITY OF TOKUSHIMA|
SUMITANI Koji THE TOKUSHIMA UNIVERSITY,SCHOOL OF DENTISTRY,ASSISTANT PROFESSOR, 歯学部・附属病院, 講師 (30206586)
HIURA Kenji THE TOKUSHIMA UNIVERSITY,SCHOOL OF DENTISTRY,ASSISTANT PROFESSOR, 歯学部・附属病院, 講師 (20228696)
上岡 寛 徳島大学, 歯学部, 助手 (80253219)
|Project Period (FY)
1995 – 1996
Completed(Fiscal Year 1996)
|Budget Amount *help
¥7,500,000 (Direct Cost : ¥7,500,000)
Fiscal Year 1996 : ¥1,500,000 (Direct Cost : ¥1,500,000)
Fiscal Year 1995 : ¥6,000,000 (Direct Cost : ¥6,000,000)
|Keywords||osteoclast (s) / osteoblast (s) / bone resorption / MC3T3-E1 / カテプシンL / プロトンポンプ / carbonic anhydrase II|
In this study, we examined the biological controls of osteoblasts to osteoclasts in the activation and formation. To examine them, we used a culture system as follows,
(1) unfractionated cells obtained from mouse long bones for osteoclastic formation
(2) stromal cell free hematopoietic blast cells (mouse) for multinucleated cell formation
(3) cloned mouse osteoblastic cells (MC3T3-E1)
The results were obtained as follows,
1) The conditioned medium (CM) of MC3T3-E1 cells precultured for 3days contained only the inhibitory factor of multinucleated cell formation. On the other hand, both inhibitory factor and stimulatory factor were found in the CM of MC3T3-E1 cells precultured for 60days. No such effectors were found in the CM of fibroblasts.
2) The production of inhibitory and stimulatory factors were depressed by indomethacin and cycloheximide, respectively.
3) The media of MC3T3-E1 cells precultured for 3 and 60days contained prostaglandin E2 which inhibited multinucleated cell formation.
1alpha, 25 (OH)_2D_3 was essential for stimulation of MNC formation by both MC3T3-E1 cells derived stimulatory factor and GM-CSF.
These results suggest that the inhibitory factor is prostaglandin E2 and the stimulatory factor is GM-CSF like protein.
5) Although TGF-beta1 has potent inhibitory effect on osteoclastic bone resorption, in the presence of 1alpha, 25 (OH)_2D_3, TGF-beta1 stimulated the formation of osteoclast.
6) TGF-beta1 inhibited multinucleated cell formation induced by 1alpha, 25 (OH)_2D_3, but the conditioned medium of TGF-beta1-treated MC3T3-E1 cells stimulated such formation.
7) Both bafilomycin A_1 (H^+-ATPase inhibitor) and acetazolamide (carbonic anhydorase II inhibitor) inhibited osteoclastic bone resorption stimulated by parathyroid hormone.
On the other hand, bafilomycin A1 did not affect procathepsin L secretion while acetazolamide inhibited the secretion.
These findings suggest that osteoblasts have the effect on osteoclastic formation through calcium regulating factors such as prostaglandin E2, GM-CSF and TGF-beta1. Less
Research Products (12results)