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.

骨骼是一种动态器官，其中矿化骨被破骨细胞不断吸收，而新骨则由成骨细胞形成。这种称为骨重塑的过程通常受到正常骨骼的维持高度调节。牙周组织和更年期的慢性感染使该过程失去平衡，并通过刺激诸如白介素-1（IL-1）和IL-6等因素的产生来增强骨骼分辨率。我们先前的研究表明，转化生长因子β（TGF-β）的成员AIVICIN A抑制了IL-1β的产生，并增强了由佛波酯和脂多糖刺激的单核细胞中IL-1受体拮抗剂的分泌。 Activin-A还抑制了各种细胞中IL-6的生物学活性。 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; BMP-2通过骨基质细胞中的破骨细胞分化因子（ODF）mRNA的积累而介导的破骨细胞形成似乎是介导的。当在M-CSF和ODF的存在下培养骨髓细胞时，激活素A可以强烈增强的破骨细胞形成。这些结果表明，TGF-β家族成员在骨质质构成中起重要作用，并且激活蛋白A的抑制剂可以用作骨质疏松症和牙周炎的治疗剂。