Transitional Growth-Associated Skeletal Stem Cells

出生后骨形成依赖于骨骼祖细胞/干细胞(SSCs)。最近进来的 活体血统追踪研究表明，SSc种群在时间和空间上- 在骨骼生长和维持过程中，受不同的SSC群体调节。在……里面 此外，有人认为生长相关的SSCs是成人的前身。 SSCS意味着在不同的祖细胞/干细胞群体之间可能存在等级关系 在这个系统中表现出高度的复杂性。鉴于此，很可能 与生长相关的SSc数量、功能或时间的中断将转化为改变 成年期的骨量。端粒酶(TERT)活性阻止细胞衰老 在再生组织中维持干细胞所需的。先前的研究表明， 端粒酶是SSC自我更新和分化所必需的。此外，还出现了 人类端粒酶活性与骨稳态下降相关，导致 骨质疏松。利用mTert-GFP和mTert-RTTA转基因报告鼠系WE 研究mTert表达细胞在出生后小鼠骨发育中的作用。 长骨的定量rna和组织学分析表明mtert表达。 主要发生在断奶时，表明这些细胞受到时间上的调节和 在骨骼快速生长和骨骼维持之间标出一个离散的发育时间点， 我们称之为“过渡性增长”。使用活体血统追踪的进一步分析 显示mTert+细胞具有骨软骨祖细胞的功能。什么生理学的 因子调节mTert+SSCs的时间模式及其在此期间的存在 特定的出生后发育阶段对于适当的成人骨骼维护至关重要 待定。因此，这项建议将1)调查两个著名的 生理生长调节因子雌激素和甲状旁腺激素对mTert+SSCs的影响 以及2)研究是否改变了这些细胞的时间模式、数量或功能 转化为成人骨骼的变化。

Postnatal bone formation relies on skeletal progenitor/stem cells (SSCs). Recent in vivo lineage-tracing studies indicate that SSC populations are temporally and spatially- regulated with distinct SSC populations functioning during bone growth and maintenance. In addition, it has been suggested that growth-associated SSCs are the predecessors to adult SSCs implying that a hierarchy may exist among the various progenitor/stem cell populations demonstrating a high degree of complexity within this system. Given this, it is likely that disruption in growth-associated SSC number, function or timing will translate into altered bone mass in adulthood. Telomerase (Tert) activity prevents cellular senescence and is required for maintenance of stem cells in regenerative tissues. Prior studies have shown that telomerase is necessary for SSC self-renewal and differentiation. In addition, decline of telomerase activity in humans correlates with a decrease in bone homeostasis leading to osteoporosis. Utilizing mTert-GFP and mTert-rtTA transgenic reporter mouse lines we investigated the role of mTert-expressing cells in postnatal mouse bone development. Quantitative RNA and histological analyses of long bones revealed that mTert is expressed predominantly at the time of weaning, suggesting these cells are temporally regulated and mark a discrete developmental time point between rapid bone growth and bone maintenance, which we have termed “transitional growth.” Further analysis using in vivo lineage-tracing showed that mTert+ cells function as osteochondral progenitor cells. What physiological factors regulate the temporal pattern of mTert+ SSCs and whether their presence during this specific postnatal developmental stage is crucial for proper adult bone maintenance remains to be determined. Therefore, this proposal will 1) investigate the effect of two well-known physiological growth-regulating factors, estrogen and parathyroid hormone, on mTert+ SSCs and 2) investigate whether altering the temporal pattern, number or function of these cells translates into changes in adult bone.