| Project/Area Number |
07457346
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Orthopaedic surgery
|
|---|
| Research Institution | University of Occupational and Environmental Health |
|---|
Principal Investigator |
NAKAMURA Toshitka University of Occupational and Environmental Health, Department of Orthopedics, Professor., 医学部, 教授 (50082235)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TANAKA Yoshiya University of Occupational and Environmental Health, The 1st Department of Inter, 医学部, 助手 (30248562)
OKABE Satoshi University of Occupational and Environmental Health, Department of Orthopedics,, 医学部, 助手 (00248577)
SAKAI Akinori University of Occupational and Environmental Health, Department of Orthopedics,, 医学部, 講師 (90248576)
|
|---|
| Project Period (FY) |
1995 – 1997
|
| Project Status |
Completed (Fiscal Year 1997)
|
| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1997: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1995: ¥3,200,000 (Direct Cost: ¥3,200,000)
|
|---|
| Keywords | Anti GP130 antibody / Interleukin-6 / Ovariectomized rats / Trabecular bone / Osteoclast / Osteoblast / Bone formation rate / Estrogen / 坐骨神経切除マウス / 骨芽細胞と破骨細胞 / 骨不動化 / 骨髄細胞 / CFU-f / CFU-GM / 副甲状腺ホルモン / 骨粗鬆症 / 骨計測 / アジュバント関節炎ラット / 挫骨神経切除マウス / カップリング異常 / 骨髄細胞の分化 |
|---|
| Research Abstract |
The results of the studies include items. The first, we clarified the changes in the bone mass, structure and mechanical properties of bone in the animal mode of osteoporosis using ovariectomized dogs and rats. Bisphosphonates blocked the osteoclastic bone resorption on the trabecular surface. The second, we investigated the abnormal bone remodeling induced by systemic inflammation using adjuvant arthritic rats model. We observed that indomathacin and methotrexate improved bone remodeling by reducing bone resorption in the animal model. Then, the third, we clarified the time-dependent changes in the bone remodeling after acute deprivation of estrogen in rats. The improvement of bone remodeling was observed by the administration of anti-human GP130 antibody which was known to inhibit the signal transduction of interleukin 6 and 11 in rat cells.
The series of these studies indicated that the increase in bone resorption was critically important for the bone loss induced by ovariectomy and systemic inflammation with polyarthritis. The increases in the cytokine productions such as IL-1, IL-6, IL-11and tumor necrosis factors were suggested to be primary carses for the signals stimulating osteoclastgenesis in the bone marrow. In inflammation induced bone loss, activated T cells were suggested to responsible to increase these cytokines. In postovariectomy bone loss, estrogen deficiency was responsible to increase the cytokines in the bone marrow, inducing the development of osteoclasts. However, our results also indicated that the regulation of some specific cytokines by using antibody may not be able to completely maintain the mass and structure of bone in these osteoporosis models. The total regulation of bone resorption would be more potent than regulating some of the osteoclast-inducing cytokines in the treatment of osteoporosis.
|
