PARATHYROID HORMONE-OSTEOBLAST MODULATED BONE RESORPTION
PARATHYROID HORMONE-OSTEOBLAST MODULATED BONE RESORPTION
批准号:
3157140
负责人:
HORACE M PERRY
金额:
$8.79万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1985
资助国家:
美国
项目状态:
已结题
起止时间:
1985-04-01 至 1988-03-31
关键词:
androgens cell differentiation dexamethasone estrogens extracellular matrix hormone regulation /control mechanism immunofluorescence technique macrophage monoclonal antibody organ culture osteoblasts osteoclast activating factor osteoclasts parathyroid hormones physiologic bone resorption prolactin radioimmunoassay surface antigens tissue /cell culture vitamin D
中文摘要
骨量减少是老年人发病和死亡的主要原因。
然而,其确切的病理生理学仍不清楚。自骨
随着个体年龄的增长,吸收增加,控制
破骨细胞是骨骼的主要吸收细胞,具有巨大的
重要性。尽管有这些观察,骨骼
寻找药物,如甲状旁腺激素(PTH),激活破骨细胞
未知。从理论上讲,这种药剂可以通过1)直接的
与破骨细胞的相互作用,2)促进分化
破骨细胞前体或3)与中间体(调节物)的相互作用
细胞反过来可以刺激破骨细胞活动和/或促进
破骨细胞分化。现有证据表明甲状旁腺
荷尔蒙通过调节细胞促进吸收。我们建议
成骨细胞具有调节甲状旁腺激素诱导的骨的能力
吸收是因为1)它们产生刺激破骨细胞的物质,2)
成骨细胞结合甲状旁腺激素,并对激素和
3)分离的巨噬细胞(代理破骨细胞)的骨吸收不是
由甲状旁腺素刺激,除非成骨细胞也存在。这项建议
旨在研究甲状旁腺激素
刺激成骨细胞调节的骨吸收。初步研究将
解决分离成骨细胞产生的因子以响应
甲状旁腺激素,能够增加骨吸收。其他
研究将探讨这种效应发生的机制
在生化和细胞水平上。这些研究还将涉及
其他激素对成骨细胞这一反应的调节作用
调节吸收细胞的反应。这些实验将
关注已知的各种细胞类型的属性
增强其降解骨基质的能力。这些属性包括)
促进未成熟巨噬细胞的分化,b)增强
吸收巨噬细胞与骨结合的能力,c)增强
巨噬细胞多核;d)巨噬细胞数量增加。
英文摘要
Osteopenia is a major cause of morbidity and mortality in an aging
population, yet its precise pathophysiology remains unclear. Since bone
resorption increases as individuals age, the mechanism of control of the
osteoclast, the primary resorbing cell of the skeleton, is of tremendous
importance. Despite these observations, the mechanisms by which bone
seeking agents, such as parathyroid hormone (PTH), activate osteoclasts are
unknown. Such agents can theoretically stimulate resorption by 1) a direct
interaction with osteoclasts, 2) enhancement of differentiation of
osteoclast precursors or 3) interaction with an intermediary (modulator)
cell which can in turn stimulate osteoclastic activity and/or promote
osteoclast differentiation. Available evidence suggests that parathyroid
hormone enhances resorption via modulator cells. We propose that
osteoblasts have the capacity to modulate parathyroid hormone induced bone
absorption because 1) they produce agents which stimulate osteoclasts, 2)
osteoblasts bind parathyroid hormone and are responsive to the hormone and
3) bone resorption by isolated macrophages (surrogate osteoclasts) is not
stimulated by the PTH unless osteoblasts are also present. This proposal
is directed toward examining the mechanisms by which parathyroid hormone
stimulates osteoblast modulated bone resorption. The initial studies will
address the isolation of the factor produced by osteoblasts in response to
parthyroid hormone which is capable of increasing bone resorption. Other
studies will address the mechanisms by which this effect takes place both
at a biochemical and cellular level. The studies will also address the
modulation of this response in osteoblasts by other hormones as well as the
modulation of the response of the resorbing cell. These experiments will
focus on the properties of the various cell types which are known to
enhance their capacity to degrade bone matrix. These properties include a)
enhance differentiation of immature macrophages, b) enhancement of the
capacity of resorptive macrophages to bind the bone, c) enhanced
multinucleation of macrophages and d) increased macrophage number.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
GENDER, MODERATE ETHANOL INTAKE AND BONE METABOLISM
-
批准号:2894146
-
项目类别:
-
资助金额:$20.84万
-
财政年份:1997
-
负责人:HORACE M PERRY
-
依托单位:
GENDER, MODERATE ETHANOL INTAKE AND BONE METABOLISM
-
批准号:2769182
-
项目类别:
-
资助金额:$22.53万
-
财政年份:1997
-
负责人:HORACE M PERRY
-
依托单位:
GENDER, MODERATE ETHANOL INTAKE AND BONE METABOLISM
-
批准号:6371397
-
项目类别:
-
资助金额:$15.79万
-
财政年份:1997
-
负责人:HORACE M PERRY
-
依托单位:
GENDER, MODERATE ETHANOL INTAKE AND BONE METABOLISM
-
批准号:6168332
-
项目类别:
-
资助金额:$21.42万
-
财政年份:1997
-
负责人:HORACE M PERRY
-
依托单位:
GENDER, MODERATE ETHANOL INTAKE AND BONE METABOLISM
-
批准号:2405788
-
项目类别:
-
资助金额:$19.96万
-
财政年份:1997
-
负责人:HORACE M PERRY
-
依托单位:
PROSPECTIVE PILOT STUDY OF ETHANOL AND BONE METABOLISM
-
批准号:2045866
-
项目类别:
-
资助金额:$5.94万
-
财政年份:1994
-
负责人:HORACE M PERRY
-
依托单位:
PROSPECTIVE PILOT STUDY OF ETHANOL AND BONE METABOLISM
-
批准号:2045867
-
项目类别:
-
资助金额:$5.96万
-
财政年份:1994
-
负责人:HORACE M PERRY
-
依托单位:
IN VIVO STUDIES OF ETHANOL AGING AND OSTEOPENIA
-
批准号:3422052
-
项目类别:
-
资助金额:$5.89万
-
财政年份:1991
-
负责人:HORACE M PERRY
-
依托单位:
IN VIVO STUDIES OF ETHANOL AGING AND OSTEOPENIA
-
批准号:2044697
-
项目类别:
-
资助金额:$5.89万
-
财政年份:1991
-
负责人:HORACE M PERRY
-
依托单位:
PARATHYROID HORMONE-OSTEOBLAST MODULATED BONE RESORPTION
-
批准号:3157139
-
项目类别:
-
资助金额:$7.83万
-
财政年份:1985
-
负责人:HORACE M PERRY
-
依托单位:
PARATHYROID HORMONE-OSTEOBLAST MODULATED BONE RESORPTION
-
批准号:3153830
-
项目类别:
-
资助金额:$8.19万
-
财政年份:1985
-
负责人:HORACE M PERRY
-
依托单位:
PARATHYROID HORMONE LYMPHOCYTE AND BONE RESORPTION
-
批准号:3446287
-
项目类别:
-
资助金额:$5.13万
-
财政年份:1983
-
负责人:HORACE M PERRY
-
依托单位:
PARATHYROID HORMONE LYMPHOCYTE AND BONE RESORPTION
-
批准号:3446011
-
项目类别:
-
资助金额:$4.9万
-
财政年份:1983
-
负责人:HORACE M PERRY
-
依托单位:
PARATHYROID HORMONE-OSTEOBLAST-MODULATED BONE RESORPTION
-
批准号:3889490
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:HORACE M PERRY
-
依托单位:
海外基金