Developmental Biology of Hard Tissue, Graduate School of Dental Medicine and Faculty of Dental Medicine, Hokkaido University, Sapporo, Japan.
Department of Endodontics and Operative Dentistry, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Oral Biosci. 2022 Sep;64(3):329-336. doi: 10.1016/j.job.2022.05.003. Epub 2022 May 15.
To verify the biological effects of parathyroid hormone (PTH) on the blood vessels in the bone, this study aimed to investigate histological alterations in endomucin-positive blood vessels and perivascular cells in murine femora after intermittent PTH administration. For comparison with blood vessels in the bone, we examined the distribution of endomucin-positive blood vessels and surrounding αSMA-immunoreactive perivascular cells in the liver, kidney, and aorta with or without PTH administration.
Six-week-old male C57BL/6J mice received hPTH [1-34] or vehicle for two weeks. All mice were fixed with a paraformaldehyde solution after euthanasia, and the right femora, kidney, liver, and aorta were extracted for immunohistochemical analysis of endomucin, αSMA, ephrinB2, EphB4, and HIF1α. Light microscopic observations of semi-thin sections and transmission electron microscopic (TEM) observations of ultra-thin sections were performed on the left femora.
After intermittent PTH administration, αSMA-reactive/ephrinB2-positive stromal cells appeared around endomucin-positive/EphB4-immunoreactive blood vessels in the bone. In addition, intense immunoreactivities of EphB4 and HIF1α were seen in vascular endothelial cells after the PTH treatment. Several stromal cells surrounding PTH-treated blood vessels exhibited well-developed rough endoplasmic reticulum under TEM observations. In contrast to bone tissues, αSMA-positive stromal cells did not increase around the endomucin-positive blood vessels in the kidney, liver, or aorta, even after PTH administration.
These findings show that intermittent PTH administration increases αSMA-reactive/ephrinB2-positive perivascular stromal cells in bone tissue but not in the kidney, liver, or aorta, suggesting that PTH preferentially affects blood vessels in the bone.
验证甲状旁腺激素（PTH）对骨骼血管的生物学效应，本研究旨在研究间歇性 PTH 给药后小鼠股骨中内皮素阳性血管和血管周细胞的组织学改变。为了与骨骼中的血管进行比较，我们检查了给予或不给予 PTH 后肝脏、肾脏和主动脉中内皮素阳性血管和周围的αSMA 免疫反应性血管周细胞的分布。
6 周龄雄性 C57BL/6J 小鼠接受 hPTH[1-34]或载体治疗两周。所有小鼠在安乐死后用多聚甲醛溶液固定，提取右侧股骨、肾脏、肝脏和主动脉进行内皮素、αSMA、ephrinB2、EphB4 和 HIF1α 的免疫组织化学分析。对左侧股骨进行半薄切片的光镜观察和超微结构的透射电镜（TEM）观察。
间歇性 PTH 给药后，骨骼中内皮素阳性/ EphB4 免疫反应性血管周围出现 αSMA 反应性/ephrinB2 阳性基质细胞。此外，PTH 治疗后血管内皮细胞中 EphB4 和 HIF1α 的免疫反应性增强。在 TEM 观察下，围绕 PTH 处理血管的一些基质细胞表现出发达的粗面内质网。与骨骼组织不同，即使给予 PTH，肾脏、肝脏或主动脉中内皮素阳性血管周围的αSMA 阳性基质细胞也没有增加。
这些发现表明，间歇性 PTH 给药增加了骨骼组织中 αSMA 反应性/ephrinB2 阳性血管周基质细胞，但在肾脏、肝脏或主动脉中没有增加，提示 PTH 优先影响骨骼中的血管。
