MECHANICAL LOADING AND PTH INTERACTIONS IN BONE

描述（改编自申请人摘要）：本研究提出， 使用非侵入性的体内模型，用于在以下情况下的应变应用： 大鼠 它旨在检查和比较间歇性甲状旁腺 激素（PTH）给药和骨内膜机械负荷 阵 它假设有一个共同的合成代谢途径， 骨对PTH和机械负荷的反应。 它将检验三个假设 在大鼠体内研究中：1）PTH调节 骨组织对机械刺激的反应; 2）PTH和机械负荷 通过两种途径调节骨生成，即，一个包括细胞 增殖，一个没有;和3）一氧化氮和 肾上腺素是参与合成代谢作用的常见旁分泌因子 机械负荷和PTH。 骨组织形态计量学将用于 测量骨形成率;溴脱氧尿苷的免疫组织化学， 测量细胞分裂;和血清生化测量血液化学， 甲状旁腺激素水平。 拟议的研究旨在为以下方面奠定基础： 定向研究旁分泌因子和细胞机制 参与了老鼠骨骼中的合成代谢反应 目前的研究是 针对表征细胞事件后， 合成代谢刺激和旁分泌（一氧化氮和 可能参与合成代谢反应。 一旦 参与合成代谢反应的细胞群和旁分泌因子是 确定，进一步的研究可以做评估细胞间旁分泌 通讯，受体表达等。如果PTH共享一个共同的合成代谢 机械负载的通路，该通路可能可以进入 直接使用定制分子，而不是间接使用系统性 激素或机械负荷。 因此，有人建议， 对合成代谢对骨骼影响的研究可能最终会导致新的 用于治疗骨质疏松症的治疗剂。

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.