ACTIVIN, INHIBIN AND FOLLISTATIN AND OSTEOBLASTOGENESIS
激活素、抑制素、卵泡抑素和成骨细胞生成
基本信息
- 批准号:2758996
- 负责人:
- 金额:$ 20.35万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-02-15 至 2004-01-31
- 项目状态:已结题
- 来源:
- 关键词:SDS polyacrylamide gel electrophoresis athymic mouse autoradiography bone marrow cell growth regulation densitometry enzyme linked immunosorbent assay follistatin hormone regulation /control mechanism immunocytochemistry immunoprecipitation inhibin laboratory mouse mixed tissue /cell culture molecular cloning osteoblasts osteoclasts osteogenesis physiologic bone resorption protein kinase radioimmunoassay receptor expression western blottings
项目摘要
Activins (ACTs) are growth factors in the TGFbeta superfamily whose
effects are antagonized by inhibin (INH) and follistatin (FS) through
different mechanisms. Although these components comprise a complex
interactive regulatory loop in the anterior pituitary to exert
endocrine, paracrine, and autocrine regulation of follicle stimulating
hormone (FSH) production, the contribution of these molecules to bone
remodeling has not been previously addressed. Preliminary results
leading to this application demonstrate that INH suppression of
osteoblastogenesis in ex vivo marrow cultures is also associated with
the inhibition of osteoclastogenesis. ACT, on the other hand, promotes
both osteoclastogenesis and osteoblastogenesis. Results also show a
differential effect of inhibin and follistatin on osteoblastogenesis and
osteoclastogenesis: INH acts on early osteoblast progenitors to prevent
their commitment to pre-osteoblasts capable of expressing alkaline
phosphatase (AP). INH suppression of osteoblastogenesis is associated
with decreased osteoclastogenesis. Significantly, the maintenance of
the early INH effect in the presence of exogenous ACT is demonstration
of uniquely INH-specific effect which is unopposed by ACT, and is a
likely mediated by INH-specific binding sites. FS prevents the full
differentiation of committed pre-osteoblasts expressing AP to
osteoblasts producing mineralized matrix, but does not suppress
osteoclast development in primary bone marrow cultures. These in vitro
effects are completely consistent with the presence of ovarian inhibin
in the circulation (and thus accessible to bone marrow) serving to limit
ACT-stimulated bone turnover in intact mice and in cycling women. Thus,
the current studies will test the hypotheses that an integrated loop,
similar to that regulating pituitary FSH, exists within the bone marrow
to regulate bone remodeling, whereby the stimulatory effect of locally
produced ACT is modulated by endocrine-derived INH and bone marrow-
derived FS. Loss of gonadal INH by gonadectomy should increase tonic
ACT action in the marrow, resulting in increased bone turnover. To test
these hypotheses, experiments will define the temporal expression of and
sensitivity to ACT, INH, and FS which lead to stage-specific effects on
bone marrow osteoblastogenesis and osteoclastogenesis; determine the
extent to which these effects are targeted directly toward cells of the
osteoblast lineage; and determine the physiological relevance of these
agents on bone turnover in vivo. The definition of the combined and
respective contributions of these hormones during mouse
osteoblastogenesis will provide insight into their potentially similar
roles in cycling and post-menopausal women.
激活素(ACTs)是转化生长因子β超家族中的生长因子,其
抑制素(INH)和卵泡抑素(FS)通过
不同的机制。尽管这些组件构成了一个复杂的
交互调节环在垂体前叶中发挥作用
卵泡刺激的内分泌、旁分泌和自分泌调节
激素(FSH)的产生,这些分子对骨骼的贡献
重塑之前并未得到解决。初步结果
导致这一应用表明异烟肼抑制
体外骨髓培养中成骨细胞的形成也与
破骨细胞生成的抑制。另一方面,法案促进了
破骨细胞形成和成骨细胞形成。结果还显示,
抑制素和卵泡抑素对成骨细胞生成的不同影响
破骨细胞生成:异烟肼作用于早期成骨细胞前体细胞,以防止
他们对能够表达碱性的前成骨细胞的承诺
磷酸酶(AP)。胰岛素对成骨细胞生成的抑制作用相关
破骨细胞生成减少。值得注意的是,维护
外源性ACT存在的早期异烟肼效应是明显的
具有独特的异烟肼特有的效果,这是ACT没有反对的,是一种
可能是由异烟肼特异性结合位点介导的。FS防止完全
表达AP的定向前成骨细胞向成骨细胞分化
成骨细胞产生矿化基质,但不抑制
原代骨髓培养中破骨细胞的发育。这些是体外培养的
其作用与卵巢抑制素的存在完全一致
在循环中(因此可进入骨髓)起限制作用的
ACT能刺激正常小鼠和骑自行车的女性的骨转换。因此,
目前的研究将检验这样的假设,即一个完整的环路,
与调节脑下垂体促卵泡激素类似,存在于骨髓中
调节骨改建,从而起到局部的刺激作用
产生的ACT受内分泌来源的异烟肼和骨髓-
派生FS。性腺切除后失去性腺激素应该会增加紧张感
作用于骨髓,增加骨骼的周转率。为了测试
这些假设、实验将定义和的时间表达式
对ACT、INH和FS的敏感性,导致对
骨髓成骨细胞和破骨细胞形成;测定
这些效应直接针对细胞的程度
成骨细胞谱系;并确定这些细胞的生理相关性
活体中骨转换剂。合并和合并的定义
这些激素在小鼠体内的各自作用
成骨细胞的形成将提供对它们潜在相似之处的洞察
在骑自行车和绝经后妇女中的作用。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Dana Gaddy其他文献
Dana Gaddy的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Dana Gaddy', 18)}}的其他基金
Inhibin Anbolism During Distraction Osteogenesis
牵张成骨过程中的抑制素代谢
- 批准号:
7449520 - 财政年份:2007
- 资助金额:
$ 20.35万 - 项目类别:
Inhibin Anbolism During Distraction Osteogenesis
牵张成骨过程中的抑制素代谢
- 批准号:
7262898 - 财政年份:2007
- 资助金额:
$ 20.35万 - 项目类别:
Inhibin Anbolism During Distraction Osteogenesis
牵张成骨过程中的抑制素代谢
- 批准号:
7484898 - 财政年份:2007
- 资助金额:
$ 20.35万 - 项目类别:
ACTIVIN, INHIBIN AND FOLLISTATIN AND OSTEOBLASTOGENESIS
激活素、抑制素、卵泡抑素和成骨细胞生成
- 批准号:
6498130 - 财政年份:1999
- 资助金额:
$ 20.35万 - 项目类别:
ACTIVIN, INHIBIN AND FOLLISTATIN AND OSTEOBLASTOGENESIS
激活素、抑制素、卵泡抑素和成骨细胞生成
- 批准号:
6350702 - 财政年份:1999
- 资助金额:
$ 20.35万 - 项目类别:
ACTIVIN, INHIBIN AND FOLLISTATIN AND OSTEOBLASTOGENESIS
激活素、抑制素和卵泡抑素与成骨细胞生成
- 批准号:
6628544 - 财政年份:1999
- 资助金额:
$ 20.35万 - 项目类别:
ACTIVIN, INHIBIN AND FOLLISTATIN AND OSTEOBLASTOGENESIS
激活素、抑制素、卵泡抑素和成骨细胞生成
- 批准号:
6150641 - 财政年份:1999
- 资助金额:
$ 20.35万 - 项目类别:
ACTIVIN AND INHIBIN-REGULATED TRANSCRIPTION OF FSH-BETA
激活素和抑制素调节的 FSH-β 转录
- 批准号:
2195881 - 财政年份:1994
- 资助金额:
$ 20.35万 - 项目类别:
相似海外基金
REPRODUCTION AND ENDOCRINE LEVELS IN THE ATHYMIC MOUSE
无胸腺小鼠的繁殖和内分泌水平
- 批准号:
3056554 - 财政年份:1990
- 资助金额:
$ 20.35万 - 项目类别:
REPRODUCTION AND ENDOCRINE LEVELS IN THE ATHYMIC MOUSE
无胸腺小鼠的繁殖和内分泌水平
- 批准号:
3056556 - 财政年份:1989
- 资助金额:
$ 20.35万 - 项目类别:
REPRODUCTION AND ENDOCRINE LEVELS IN THE ATHYMIC MOUSE
无胸腺小鼠的繁殖和内分泌水平
- 批准号:
3056555 - 财政年份:1988
- 资助金额:
$ 20.35万 - 项目类别:
REPRODUCTION AND ENDOCRINE LEVELS IN THE ATHYMIC MOUSE
无胸腺小鼠的繁殖和内分泌水平
- 批准号:
3056553 - 财政年份:1987
- 资助金额:
$ 20.35万 - 项目类别:
The Athymic Mouse As a Model For the Study of Keloids
无胸腺小鼠作为瘢痕疙瘩研究的模型
- 批准号:
7816691 - 财政年份:1978
- 资助金额:
$ 20.35万 - 项目类别:
Standard Grant