Intermittent parathyroid hormone administration converts quiescent lining cells to active osteoblasts.
Intermittent parathyroid hormone administration converts quiescent lining cells to active osteoblasts.
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DOI：
10.1002/jbmr.1665
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发表时间：
2012-10
影响因子：
6.2
通讯作者：
Kronenberg, Henry M.
中科院分区：
文献类型：
--
作者：
Kim, Sang Wan;Pajevic, Paola Divieti;Selig, Martin;Barry, Kevin J.;Yang, Jae-Yeon;Shin, Chan Soo;Baek, Wook-Young;Kim, Jung-Eun;Kronenberg, Henry M.
甲状旁腺激素（PTH）的间歇性管理增加骨量，至少部分，通过增加成骨细胞的数量。成骨细胞的一个可能来源可能是失活的内层细胞转化为成骨细胞，间接证据与这一假设一致。为了更好地了解甲状旁腺素对衬细胞激活的可能影响，我们利用诱导基因系统进行了谱系追踪研究。将Dmp1-CreERt2小鼠与ROSA26R报告小鼠杂交，获得X-gal染色检测到的目标成熟成骨细胞及其后代、衬细胞和骨细胞。Dmp1-CreERt2(+):ROSA26R小鼠于出生后第3、5、7、14和21天注射0.25 mg 4- oh -他莫昔芬（4-OHTam）。动物于出生后第23、33或43天（最后一次注射4-OHTam后2、12或22天）处死。第43天，小鼠皮下注射人甲状旁腺激素（1 - 34,80 μg/kg）或对照物，每天1次，连续3天。最后一次注射4-OHTam后22天，颅骨和胫骨骨膜表面大部分X-gal（+）细胞呈扁平状。与第23天相比，第43天骨形成率和胶原I(α1) mRNA表达降低。注射PTH 3天后，X-gal（+）细胞厚度增加，骨钙素和胶原I(α1) mRNA表达增加。电镜显示，在给药前的薄细胞和给药后的立方细胞中都有x -gal相关的染色质颗粒。这些数据支持了间断性甲状旁腺激素治疗可以通过在体内将衬细胞转化为成熟成骨细胞来增加成骨细胞数量的假设。
Intermittent administration of parathyroid hormone (PTH) increases bone mass, at least in part, by increasing osteoblast number. One possible source of osteoblasts might be conversion of inactive lining cells to osteoblasts, and indirect evidence is consistent with this hypothesis. To better understand the possible effect of PTH on lining cell activation, a lineage tracing study was conducted using an inducible gene system. Dmp1-CreERt2 mice were crossed with ROSA26R reporter mice to render targeted mature osteoblasts and their descendents, lining cells and osteocytes, detectable by X-gal staining. Dmp1-CreERt2(+):ROSA26R mice were injected with 0.25 mg 4-OH-tamoxifen (4-OHTam) on postnatal day 3, 5, 7, 14, and 21. The animals were sacrificed on postnatal day 23, 33 or 43 (2, 12 or 22 days after the last 4-OHTam injection). On day 43, mice were challenged with a subcutaneous injection of human PTH (1–34, 80 μg/kg) or vehicle once daily for 3 days. By 22 days after the last 4-OHTam injection, most X-gal (+) cells on the periosteal surfaces of both the calvaria and tibia were flat. Moreover, bone formation rate and collagen I(α1) mRNA expression were decreased at day 43 compared to day 23. After 3 days of PTH injections, the thickness of X-gal (+) cells increased, as did their expression of osteocalcin and collagen I(α1) mRNA. Electron microscopy revealed X-gal-associated chromagen particles in both thin cells prior to PTH administration and cuboidal cells following PTH administration. These data support the hypothesis that intermittent PTH treatment can increase osteoblast number by converting lining cells to mature osteoblasts in vivo.
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影响因子：
4.1
作者：
Jilka, Robert L.;O'Brien, Charles A.;Ali, A. Afshan;Roberson, Paula K.;Weinstein, Robert S.;Manolagas, Stavros C.
通讯作者：
Manolagas, Stavros C.
影响因子：
4.1
作者：
Fox, J.;Miller, M. A.;Smith, S. Y.
通讯作者：
Smith, S. Y.
影响因子：
6.2
作者：
Gluhak-Heinrich, J;Ye, L;Pavlin, D
通讯作者：
Pavlin, D
影响因子：
6.2
作者：
Everts, V;Delaissé, JM;Beertsen, W
通讯作者：
Beertsen, W
影响因子：
4.1
作者：
Kalajzic, I;Braut, A;Rowe, DW
通讯作者：
Rowe, DW