CYTOPLASMIC CA++ AND BONE MECHANICAL/CHEMICAL COUPLING

细胞质 CA 和骨机械/化学耦合

• 批准号: 2131891
• 负责人: KENNETH W SNOWDOWNE
• 金额: $ 3.38万
• 依托单位: UNIVERSITY OF THE PACIFIC-SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2131891
• 关键词: biological signal transduction; calcium channel; calcium channel blockers; calcium flux; cell osmotic pressure; electrical conductance; embryo /fetus tissue /cell culture; hormone regulation /control mechanism; laboratory rat; membrane potentials; osteoblasts

Orthodontic tooth movement requires the precise application of force directed towards moving the tooth through the alveolar bone along the dental arch. Orthodontic tooth movement is thus an example of directed bone remodeling, i.e., the imposition of external forces to reshape bone is made possible by the "biological plasticity" of bone. The biological plasticity of bone is made possible by the coordinated activities of osteoblasts and osteoclasts in the alveolar bone that somehow respond to this external force. We propose that a calcium-conducting stretch channel in the surface membrane of osteoblasts is the mechanical transducer responsible for detecting force and converting its energy into a biological response. We shall show that very small changes in osmotic pressure (i.e., < 5%), which open stretch channels in other cells, cause a significant increase in cytoplasmic calcium (Ca) - a well-known second messenger that is responsible for activating osteoblasts. The effect of osmotic-evoked stretches of the surface membrane on Ca is reproducible and fully reversible. Moreover, this rise in Ca disappears when extracellular calcium is removed, suggesting that this osmotic-induced rise in Ca is due to an influx of Ca. Our goal is to characterize this channel in the osteoblast-like cells (NC3T-E1), as well as osteoblasts isolated from fetal rat calvaria, discover specific inhibitors, and investigate its hormonal sensitivity. Understanding how this channel works will not only establish how orthodontists are able to move teeth, but will also contribute to our understanding of osseo-integration of dental implants, maxillofacial development, and the effects of gravity on the skeleton.

正畸牙齿移动需要精确的用力 旨在沿着牙槽骨移动牙齿 牙弓。 因此，正畸牙齿移动是定向的一个例子 骨重塑，即施加外力来重塑骨 骨骼的“生物可塑性”使之成为可能。 生物的 骨骼的可塑性是通过协调活动而成为可能的 牙槽骨中的成骨细胞和破骨细胞以某种方式响应 这个外力。 我们建议钙传导拉伸 成骨细胞表面膜上的通道是机械通道 传感器负责检测力并将其能量转换为 一种生物反应。 我们将证明渗透压的微小变化 压力（即 < 5%）会打开其他细胞中的拉伸通道，导致 细胞质钙 (Ca) 显着增加 - 众所周知的第二个 负责激活成骨细胞的信使。 的效果 Ca 表面膜的渗透诱发拉伸是可重复的 并且完全可逆。 此外，当 细胞外钙被去除，表明这种渗透诱导的 Ca 的增加是由于 Ca 的流入。 我们的目标是描述这一点 成骨细胞样细胞 (NC3T-E1) 以及成骨细胞中的通道 从胎鼠颅骨中分离，发现特异性抑制剂，以及 研究其荷尔蒙敏感性。 了解该频道如何 作品不仅将确定正牙医生如何移动牙齿， 但也将有助于我们对骨整合的理解 牙种植体、颌面发育和重力的影响 骷髅上。