THE EFFECTS OF INHIBITORS OF OSTEOCLASTC BONE RESORPTION IN GIANT CELL TUMOR

破骨细胞骨吸收抑制剂对巨细胞瘤的影响

• 批准号: 11671443
• 负责人: YOSHIDA Seiji
• 金额: $ 0.32万
• 依托单位: OITA MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671443/
• 关键词: Giant cell tumor; Bisphosphonate; Estrogen; TRAP; TRAP

Bisphosphonates inhibit bone resorption and are therapeutically effective in diseases of increased bone turnover, such as Paget's disease and hypercalcemia of malignancy. The mechanisms by which they act remain unclear. Proposed mechanisms include inhibition of osteoclast formation from precursors and inhibitory or toxic effect on mature osteoclasts. We have developed a new in vitro model to study osteoclast survival and in this paper that may explain both the observed reduction in osteoclast numbers and in bone resorption by mature osteoclasts, namely that bisphosphonates induce programd cell death (apoptosis). Three bisphosphonates caused a 4- to 24-fold increase in the proportion of osteoclasts showing the characteristic morphology of apoptosis in vitro. Of the three compounds, risedronate, the most potent inhibitor of bone resorption in vivo, was the strongest inducer of osteoclast apoptosis in vitro. Osteoclast apoptosis may therefore be a major mechanism whereby bisphosphonates reduce osteoclast numbers and activity, and induction of apoptosis could be a therapeutic goal for new antiosteoclast drugs.

双膦酸盐抑制骨吸收，对骨转换增加的疾病，如佩吉特病和恶性高钙血症有治疗效果。它们的作用机制尚不清楚。提出的机制包括抑制破骨细胞形成的前体和抑制或毒性作用成熟的破骨细胞。我们开发了一种新的体外模型来研究破骨细胞的存活，并在本文中解释了观察到的破骨细胞数量减少和成熟破骨细胞骨吸收减少，即双膦酸盐诱导程序性细胞死亡（凋亡）。三种双膦酸盐引起体外破骨细胞比例增加4 ~ 24倍，表现出细胞凋亡的特征形态。在这三种化合物中，体内最有效的骨吸收抑制剂利塞膦酸盐是体外最强的破骨细胞凋亡诱导剂。因此，破骨细胞凋亡可能是双膦酸盐降低破骨细胞数量和活性的主要机制，诱导细胞凋亡可能是新的抗破骨细胞药物的治疗目标。

项目成果

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S. YOSHIDA 等人：“胫神经内特发性异位骨化。J.B.J.S.”（正在出版）。

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M.Ktaoka 等人：“骨髓炎肉芽组织中的多核细胞极”Acta Orthop Scand。

M.Kataoka, et al.: "An Assessment of Histpathological Critenia for Infection in Joint Arthroplasty in Pheumatoid Synoviam"Clinical Pheumatology. (in press). (2002)

M.Kataoka 等人：“风湿性滑膜炎关节置换术中感染的组织病理学标准的评估”临床风湿病学。

S.Yoshida, et al.: "Idiopathic heterotopic Ossification within the tibial nerve"J.B.J.S, American volume. (in press). (2002)

S.Yoshida 等：“胫神经内特发性异位骨化”J.B.J.S，美国卷。

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M. KATAOKA 等人：“多核细胞在骨髓炎颗粒组织中的作用”Acta Orthop Scand。