The effect of activin A, an antagonist of IL-1 and IL-6, on osteoclast formation.

激活素 A（IL-1 和 IL-6 的拮抗剂）对破骨细胞形成的影响。

基本信息

批准号：
10557169
负责人：
YAMATO Kenji
金额：
$ 5.06万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10557169/
关键词：
activin osteoclast BMP TGF-β IL-1 vitamin D3 ODF 骨芽細胞骨吸収 IL-1α プロスタグランジンE2

项目摘要

The skeleton is a dynamic organ in which mineralized bone is continuously resorbed by osteoclasts, and new bone is formed by osteoblasts. This process, known as bone remodeling, is normally highly regulated with maintenance of a normal amount of bone. Chronic infection of the periodontal tissue and menopause put the process out of balance and enhance bone resorption by stimulating production of factors such as interleukin-1 (IL-1) and IL-6. Our previous study demonstrated that activin A, a member of transforming growth factor beta (TGF-β), inhibited the production of IL-1β and enhanced secretion of IL-1 receptor antagonist in monocytic cells stimulated by phorbol ester and lipopolysaccharide. Activin-A also inhibits the biological activities of IL-6 in various types of cells. In this study, we examined the role of TGF-β family members including activin-A in the osteoclast formation and obtained interesting results as follows : when mouse bone marrow cells were co-cultured with bone stromal cells, all the TGF-β family members tested (TGF-β1, activin-A, BMP-2) stimulated vitamin D3- and IL-1α-mediated osteoclast formation ; enhancement of osteoclast formation by BMP-2 appeared to be mediated through accumulation of osteoclast differentiation factor (ODF) mRNA in bone stromal cells ; when bone marrow cells were cultured in the presence of M-CSF and ODF, activin-A strongly enhanced osteoclast formation. These results suggest that TGF-β family members play an important role in osteoclastogenesis and that inhibitors of activin-A can be used as a therapeutic agent of osteoporosis and periodontitis.

骨骼是一个动态器官，其中矿化骨不断被破骨细胞吸收，并且新骨由成骨细胞形成，这一过程被称为骨重塑，通常受到牙周慢性感染的正常数量的调节。组织和更年期使这一过程失去平衡，并通过刺激白细胞介素 1 (IL-1) 和 IL-6 等因子的产生来增强骨吸收。我们之前的研究表明，激活素 A（转化因子的成员之一）。生长因子β (TGF-β)，抑制佛波酯和脂多糖刺激的单核细胞中IL-1β的产生并增强IL-1受体拮抗剂的分泌，还抑制各种类型的IL-6的生物活性。在这项研究中，我们检查了 TGF-β 家族成员（包括激活素 A）在破骨细胞形成中的作用，并获得了如下有趣的结果：当小鼠骨髓细胞共培养时。对于骨基质细胞，所有测试的 TGF-β 家族成员（TGF-β1、激活素 A、BMP-2）均刺激维生素 D3 和 IL-1α 介导的破骨细胞形成，BMP-2 似乎能增强破骨细胞形成；通过破骨细胞分化因子 (ODF) mRNA 在骨基质细胞中的积累介导；当骨髓细胞在 M-CSF 和 ODF 存在的情况下培养时，激活素 A 会强烈增强破骨细胞的作用；这些结果表明TGF-β家族成员在破骨细胞生成中发挥重要作用，并且激活素A的抑制剂可用作骨质疏松症和牙周炎的治疗剂。