Department of Kinesiology, University of Texas at Arlington, Arlington, TX, USA.
Exp Physiol. 2020 Jul;105(7):1159-1171. doi: 10.1113/EP087869. Epub 2020 May 26.
What is the central question of this study? We sought to assess the effects of intermittent parathyroid hormone (1-34) administration on bone angiogenesis, the redistribution of bone marrow blood vessels, and matrix metalloproteinase 9 as a function of advancing age in mice. What is the main finding and its importance? Short-term (i.e. 10 days) intermittent parathyroid hormone (1-34) administration increased the number of small (≤29-µm-diameter) bone marrow blood vessels and augmented matrix metalloproteinase 9. These changes occurred before alterations in trabecular bone. Given the rapid response in bone angiogenesis, this investigation highlights the impact of intermittent parathyroid hormone (1-34) administration on the bone vascular network.
Intermittent parathyroid hormone (PTH) administration augments bone, stimulates the production of matrix metalloproteinase 9 (Mmp9) and relocates bone marrow blood vessels closer to osteoid seams. Discrepancies exist, however, regarding bone angiogenesis. Given that Mmp9 participates in cellular homing and migration, it might aid in blood vessel relocation. We examined the influence of short-term intermittent PTH administration on angiogenesis, Mmp9 secretion and the distance between blood vessels and bone. Mature (6- to 8-month-old) and middle-aged (10- to 12-month-old) male and female C57BL/6 mice were divided into three groups: control (CON), and 5 (5dPTH) and 10 days (10dPTH) of intermittent PTH administration. Mice were given PBS (50 µl day ) or PTH(1-34) (43 µg kg day ). Frontal sections (5 µm thick) of the right distal femoral metaphysis were triple-immunolabelled to identify endothelial cells (anti-CD31), vascular smooth muscle cells (anti-αSMA) and Mmp9 (anti-Mmp9). Vascular density, Mmp9 density, area and localization, and blood vessel distance from bone were analysed. Blood vessels were analysed according to diameter: 1-29, 30-100 and 101-200 µm. Trabecular bone microarchitecture and bone static and dynamic properties were assessed. No main effects of age were observed for any variable. The density of CD31-labelled blood vessels 1-29 and 30-100 µm in diameter was higher (P < 0.05) and tended (P = 0.055) to be higher, respectively, in 10dPTH versus 5dPTH and CON. Mmp9 was augmented (P < 0.05) in 10dPTH versus the other groups. Mmp9 was closer (P < 0.05) to blood vessels 1-29 µm in diameter and furthest (P < 0.05) from bone. In conclusion, bone angiogenesis occurred by day 10 of intermittent PTH administration, coinciding with augmented Mmp9 secretion near the smallest blood vessels (1-29 µm in diameter).
本研究的核心问题是什么？我们旨在评估间歇甲状旁腺激素（1-34）给药对小鼠骨血管生成、骨髓血管再分布以及作为年龄增长的功能的基质金属蛋白酶 9 的影响。主要发现及其重要性是什么？短期（即 10 天）间歇甲状旁腺激素（1-34）给药增加了小（≤29-µm 直径）骨髓血管的数量，并增加了基质金属蛋白酶 9。这些变化发生在小梁骨改变之前。鉴于骨血管生成的快速反应，本研究强调了间歇甲状旁腺激素（1-34）给药对骨脉管网络的影响。
间歇甲状旁腺激素（PTH）给药可增强骨、刺激基质金属蛋白酶 9（Mmp9）的产生并使骨髓血管更靠近类骨质缝。然而，骨血管生成存在差异。鉴于 Mmp9 参与细胞归巢和迁移，它可能有助于血管再定位。我们研究了短期间歇 PTH 给药对血管生成、Mmp9 分泌以及血管与骨骼之间距离的影响。成熟（6-8 月龄）和中年（10-12 月龄）雄性和雌性 C57BL/6 小鼠分为三组：对照组（CON）和 5 天（5dPTH）和 10 天（10dPTH）间歇 PTH 给药。小鼠给予 PBS（50µl 天）或 PTH（1-34）（43µg/kg 天）。对右侧远端股骨干骺端的额部切片（5µm 厚）进行三标免疫标记以鉴定内皮细胞（抗-CD31）、血管平滑肌细胞（抗-αSMA）和 Mmp9（抗-Mmp9）。分析血管密度、Mmp9 密度、面积和定位以及血管与骨骼的距离。根据直径分析血管：1-29、30-100 和 101-200µm。评估了小梁骨微结构以及骨静态和动态特性。任何变量均未观察到年龄的主要影响。直径为 1-29 和 30-100µm 的 CD31 标记血管的密度更高（P<0.05），并且 10dPTH 与 5dPTH 和 CON 相比，分别倾向于更高（P=0.055）。Mmp9 在 10dPTH 时增加（P<0.05）。Mmp9 更靠近直径为 1-29µm 的血管（P<0.05），并且离骨骼最远（P<0.05）。总之，间歇 PTH 给药 10 天即可发生骨血管生成，这与最小血管（1-29µm 直径）附近增强的 Mmp9 分泌同时发生。
