Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, And Faculty of Dental Medicine, Hokkaido University, Sapporo, Japan.
Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, And Faculty of Dental Medicine, Hokkaido University, Sapporo, Japan; Northern Army Medical Unit, Camp Makomanai, Japan Ground Self-Defense Forces, Sapporo, Japan.
J Oral Biosci. 2022 Sep;64(3):279-286. doi: 10.1016/j.job.2022.08.002. Epub 2022 Aug 14.
The intermittent administration of parathyroid hormone (PTH) has been prescribed to osteoporotic patients due to its bone anabolic effects. In addition to its actions on bone cells, PTH appears to affect bone-specific blood vessels. These blood vessels are derived from bone marrow sinusoids, which express EphB4, a hallmark of veinous vascular endothelial cells. Given the presence of osteo-vascular interactions, it is important to elucidate the effects of PTH on bone cells and blood vessels in murine models.
PTH stimulates preosteoblastic proliferation and osteoblastic bone formation. The former appears to be directly affected by PTH, whereas the latter requires osteoclast-mediated coupling. The administration of PTH through high-frequency dosage schemes accelerates bone turnover featuring remodeling-based bone formation, whereas low-frequency schemes cause mainly remodeling-based and partly modeling-based bone formation. Normally, many blood vessels lack alpha smooth muscle actin (αSMA)-immunoreactive vascular muscle cells surrounding basement membranes, indicating them being capillaries. However, PTH administration increases the number of blood vessels surrounded by αSMA-positive cells. These αSMA-positive cells spread out of blood vessels and express alkaline phosphatase and c-kit, suggesting their potential to differentiate into osteogenic and vascular endothelial/perivascular cells. Unlike bone cells, αSMA-positive cells did not appear in the periphery of blood vessels in the kidney and liver, and the thickness of the tunica media did not change regardless of PTH administration.
Based on the results of the study and presence of osseous-vascular interactions, PTH appears to influence not only osteoblastic cells, but also blood vessels in bone.
由于甲状旁腺激素 (PTH) 具有骨合成代谢作用,因此被开给骨质疏松症患者间歇性使用。除了对骨细胞的作用外,PTH 似乎还影响骨特异性血管。这些血管来源于骨髓窦,其中表达 EphB4,这是静脉血管内皮细胞的标志。鉴于存在骨血管相互作用,阐明 PTH 对鼠模型中骨细胞和血管的影响非常重要。
PTH 刺激前成骨细胞增殖和成骨细胞骨形成。前者似乎直接受到 PTH 的影响,而后者则需要破骨细胞介导的偶联。通过高频剂量方案给予 PTH 可加速骨转换,其特征是基于重塑的骨形成,而低频方案则主要导致基于重塑和部分基于建模的骨形成。通常,许多血管缺乏围绕基底膜的α平滑肌肌动蛋白 (αSMA)-免疫反应性血管平滑肌细胞,表明它们是毛细血管。然而,PTH 给药会增加被 αSMA 阳性细胞包围的血管数量。这些 αSMA 阳性细胞从血管中扩散出来,并表达碱性磷酸酶和 c-kit,表明它们有可能分化为成骨细胞和血管内皮/血管周细胞。与骨细胞不同,αSMA 阳性细胞不会出现在肾脏和肝脏血管的外围,并且无论是否给予 PTH,血管中层的厚度都不会改变。
基于研究结果和骨血管相互作用的存在,PTH 似乎不仅影响成骨细胞,还影响骨骼中的血管。