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Intermittent PTH Administration Increases Bone-Specific Blood Vessels and Surrounding Stromal Cells in Murine Long Bones
Calcified Tissue International ( IF 3.3 ) Pub Date : 2020-11-10 , DOI: 10.1007/s00223-020-00776-2
Shen Zhao 1, 2, 3 , Tomoka Hasegawa 2 , Hiromi Hongo 2 , Tomomaya Yamamoto 4 , Miki Abe 2 , Taiji Yoshida 2 , Mai Haraguchi 2 , Paulo Henrique Luiz de Freitas 5 , Minqi Li 6 , Kanchu Tei 3 , Norio Amizuka 2
Affiliation  

To verify whether PTH acts on bone-specific blood vessels and on cells surrounding these blood vessels, 6-week-old male mice were subjected to vehicle (control group) or hPTH [1–34] (20 µg/kg/day, PTH group) injections for 2 weeks. Femoral metaphyses were used for histochemical and immunohistochemical studies. In control metaphyses, endomucin-positive blood vessels were abundant, but αSMA-reactive blood vessels were scarce. In the PTH-administered mice, the lumen of endomucin-positive blood vessels was markedly enlarged. Moreover, many αSMA-positive cells were evident near the blood vessels, and seemed to derive from those vessels. These αSMA-positive cells neighboring the blood vessels showed features of mesenchymal stromal cells, such as immunopositivity for c-kit and tissue nonspecific alkaline phosphatase (TNALP). Thus, PTH administration increased the population of perivascular/stromal cells positive for αSMA and c-kit, which were likely committed to the osteoblastic lineage. To understand the cellular events that led to increased numbers and size of bone-specific blood vessels, we performed immunohistochemical studies for PTH/PTHrP receptor and VEGF. After PTH administration, PTH/PTHrP receptor, VEGF and its receptor flk-1 were consistently identified in both osteoblasts and blood vessels (endothelial cells and surrounding perivascular cells). Our findings suggest that exogenous PTH increases the number and size of bone-specific blood vessels while fostering perivascular/stromal cells positive for αSMA/TNALP/c-kit.



中文翻译:

间歇性 PTH 给药可增加小鼠长骨中的骨特异性血管和周围基质细胞

为了验证 PTH 是否作用于骨特异性血管和这些血管周围的细胞,对 6 周大的雄性小鼠进行载体(对照组)或 hPTH [1-34](20 µg/kg/天,PTH组)注射 2 周。股骨干骺端用于组织化学和免疫组织化学研究。在对照干骺端,endomucin 阳性血管丰富,但 αSMA 反应性血管稀少。在PTH给药的小鼠中,内粘蛋白阳性血管的管腔明显扩大。此外,许多αSMA阳性细胞在血管附近很明显,并且似乎来自这些血管。这些与血管相邻的αSMA阳性细胞显示出间充质基质细胞的特征,例如对c-kit和组织非特异性碱性磷酸酶(TNALP)的免疫阳性。因此,PTH 给药增加了对 αSMA 和 c-kit 呈阳性的血管周围/基质细胞的数量,这些细胞可能致力于成骨细胞谱系。为了了解导致骨特异性血管数量和大小增加的细胞事件,我们对 PTH/PTHrP 受体和 VEGF 进行了免疫组织化学研究。在 PTH 给药后,PTH/PTHrP 受体、VEGF 及其受体 flk-1 在成骨细胞和血管(内皮细胞和周围血管周围细胞)中均得到一致鉴定。我们的研究结果表明,外源性 PTH 增加了骨特异性血管的数量和大小,同时促进了 αSMA/TNALP/c-kit 阳性的血管周围/基质细胞。为了了解导致骨特异性血管数量和大小增加的细胞事件,我们对 PTH/PTHrP 受体和 VEGF 进行了免疫组织化学研究。在 PTH 给药后,PTH/PTHrP 受体、VEGF 及其受体 flk-1 在成骨细胞和血管(内皮细胞和周围血管周围细胞)中均得到一致鉴定。我们的研究结果表明,外源性 PTH 增加了骨特异性血管的数量和大小,同时促进了 αSMA/TNALP/c-kit 阳性的血管周围/基质细胞。为了了解导致骨特异性血管数量和大小增加的细胞事件,我们对 PTH/PTHrP 受体和 VEGF 进行了免疫组织化学研究。在 PTH 给药后,PTH/PTHrP 受体、VEGF 及其受体 flk-1 在成骨细胞和血管(内皮细胞和周围血管周围细胞)中均得到一致鉴定。我们的研究结果表明,外源性 PTH 增加了骨特异性血管的数量和大小,同时促进了 αSMA/TNALP/c-kit 阳性的血管周围/基质细胞。VEGF 及其受体 flk-1 在成骨细胞和血管(内皮细胞和周围的血管周围细胞)中都得到了一致的鉴定。我们的研究结果表明,外源性 PTH 增加了骨特异性血管的数量和大小,同时促进了 αSMA/TNALP/c-kit 阳性的血管周围/基质细胞。VEGF 及其受体 flk-1 在成骨细胞和血管(内皮细胞和周围的血管周围细胞)中都得到了一致的鉴定。我们的研究结果表明,外源性 PTH 增加了骨特异性血管的数量和大小,同时促进了 αSMA/TNALP/c-kit 阳性的血管周围/基质细胞。

更新日期:2020-11-12
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