MECHANICAL LOADING AND PTH INTERACTIONS IN BONE

描述(改编自申请人的摘要)：这项研究建议 使用非侵入性的活体模型在胫骨中应用应变 老鼠。它试图检查和比较间歇性甲状旁腺的效果。 激素(PTH)给药与骨内膜骨的机械负荷 队形。它假设存在一条共同的合成代谢途径 骨对甲状旁腺素和机械负荷的反应。它将检验三个假设 在大鼠体内的研究：1)甲状旁腺激素调节 骨组织对机械刺激；2)甲状旁腺素和机械负荷 通过两条途径调节成骨，即一条包括细胞的途径 增殖，一个不会；和3)一氧化氮和 前列腺素是参与合成代谢作用的常见旁分泌因子。 机械加载和PTH。骨组织形态计量学将用于 测量骨形成率；溴脱氧尿苷免疫组织化学 测量细胞分裂；以及血清生化测量血液化学和 甲状旁腺素水平。拟议的研究旨在为以下工作奠定基础 旁分泌因子及其细胞机制的定向研究 参与大鼠骨骼的合成代谢反应。目前的研究是 旨在描述以下细胞事件的特征 合成代谢刺激与对映体的鉴定(一氧化氮和 前列腺素)，可能参与合成代谢反应。一旦 参与合成代谢反应的细胞群体和旁分泌因子有 确定后，可以进行进一步的研究以评估细胞间旁分泌 通讯、受体表达等。如果甲状旁腺激素具有共同的合成代谢 机械加载的路径，这条路径可能是可以进入的 直接使用定制分子，而不是间接使用系统 荷尔蒙或机械负荷。因此，有人建议拟议的 对合成代谢骨骼影响的研究可能最终会导致新的 治疗骨质疏松症的疗法。

DESCRIPTION (Adapted from the Applicant's Abstract): This study proposes to use a non-invasive, in vivo model for strain application in the tibiae of rats. It seeks to examine and compare effects of intermittent parathyroid hormone (PTH) administration and mechanical loading on endosteal bone formation. It hypothesizes that there is a common anabolic pathway for the bone responses to PTH and mechanical loading. It will test three hypotheses with in vivo studies in rats: 1) that PTH modulates the responsiveness of bone tissue to mechanical stimuli; 2) that PTH and mechanical loading modulate osteogenesis through two pathways, i.e., one that includes cell proliferation, one that does not; and 3) that nitric oxide and prostaglandins are common paracrine factors involved in the anabolic effects of mechanical loading and PTH. Bone histomorphometry will be used to measure bone formation rates; immunohistochemistry of bromodeoxyuridine to measure cell division; and serum biochemistry to measure blood chemistry and PTH levels. The proposed studies are intended to lay the groundwork for directed research into the paracrine factors and cellular mechanisms involved in the anabolic response in rat bone. The current studies are directed toward characterization of the cellular events following an anabolic stimulus and the identification of paracrines (nitric oxide and prostaglandins) that may be involved in the anabolic response. Once the cell populations and paracrine factors involved in the anabolic response are identified, further studies may be done to assess cell-to-cell paracrine communication, receptor expression, etc. If PTH shares a common anabolic pathway with mechanical loading, this pathway possibly could be accessed directly, with custom molecules, rather than indirectly using systemic hormones or mechanical loads. It is suggested, therefore, that the proposed research into anabolic bone effects might eventually lead to new therapeutics for treating osteoporosis.