A study on mevalonic acid pathway-targeting therapy to recovery osteoclasts damaged with bisphosphonate

甲羟戊酸途径靶向治疗双膦酸盐损伤破骨细胞恢复的研究

• 批准号: 23659957
• 负责人: IKEBE Tetsuro
• 金额: $ 2.08万
• 依托单位: Fukuoka Dental College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659957/
• 关键词: 破骨細胞; 顎骨壊死; ビスフォスフォネート; メバロン酸

Nitrogen-containing bisphosphonate (BP) is used as effective therapeutic agent for managing bone-resorbing diseases such as osteoporosis and cancer bone metastasis. It is well know n that osteonecrosis of the jaw occasionally occurs in the patients treated with nitrogen-containing bisphosphonate after tooth extraction, which is called as BRONJ. Although BRONJ is quite difficult to treat and annoys both the patients and dentists for a long time, any effective therapies for BRONJ have not been established. The target cell of BP is osteoclast. BP inhibits the mevalonic acid pathway of osteoclast to inhibit osteoclastic bone-resorbing activity. In order to recover the BP-induced inhibition of osteoclast activity, the effects of geranylgeraniol (GGOH), an intermediate of mevalonic acid pathway, on BP-induced inhibition of osteoclast activity was investigated in this study. As a result, the addition of GGOH to cultured osteoclasts restored multinucleation, TRAP expression, cell migratinability and the expression of cell fusion-promoting factor STAMP of BP-inhibited osteoclasts. This study suggests that GGOH may neutralize the adverse effects of BP in osteoclasts.

含氮双膦酸盐（BP）被用作治疗骨质疏松症和癌症骨转移等骨吸收疾病的有效治疗剂。众所周知，拔牙后接受含氮双膦酸盐治疗的患者偶尔会出现颌骨坏死，称为BRONJ。尽管BRONJ治疗起来相当困难，并且长期以来困扰着患者和牙医，但目前尚未建立任何有效的治疗BRONJ的方法。 BP的靶细胞是破骨细胞。 BP通过抑制破骨细胞的甲羟戊酸途径来抑制破骨细胞的骨吸收活性。为了恢复BP诱导的破骨细胞活性抑制，本研究研究了甲羟戊酸途径中间体香叶基香叶醇(GGOH)对BP诱导的破骨细胞活性抑制的影响。结果，在培养的破骨细胞中添加GGOH可以恢复BP抑制的破骨细胞的多核、TRAP表达、细胞迁移能力和细胞融合促进因子STAMP的表达。这项研究表明 GGOH 可以中和 BP 对破骨细胞的不利影响。

项目成果

Zoledronic acid inhibits RANK expression and migration of osteoclast precursors during osteoclastogenesis

• DOI: 10.1007/s00210-010-0596-4
• 发表时间: 2011-03-01
• 期刊: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
• 影响因子: 3.6
• 作者: Kimachi, Keiichiro;Kajiya, Hiroshi;Okabe, Koji
• 通讯作者: Okabe, Koji

NF-κB acts as a multifunctional modulator in bone invasion by oral squamous cell carcinoma.

NF-κB 在口腔鳞状细胞癌骨侵袭中充当多功能调节剂。

• DOI: 10.1016/s1348-8643
• 发表时间: 2016
• 期刊: Oral Science International
• 影响因子: 0.5
• 作者: Jimi E;Kokabu S;Matsubara T;Nakatomi C;Matsuo K;Watanabe S
• 通讯作者: Watanabe S