Intermittent PTH Administration Increases Bone-Specific Blood Vessels and Surrounding Stromal Cells in Murine Long Bones

• Published in: Calcified tissue international 2021-03, Vol.108 (3), p.391-406
• Main Authors: Zhao, Shen, Hasegawa, Tomoka, Hongo, Hiromi, Yamamoto, Tomomaya, Abe, Miki, Yoshida, Taiji, Haraguchi, Mai, de Freitas, Paulo Henrique Luiz, Li, Minqi, Tei, Kanchu, Amizuka, Norio
• Format: Article
• Language: English
• Subjects: Alkaline phosphatase; Alkaline Phosphatase - metabolism; Animals; Biochemistry; Biomedical and Life Sciences; Blood vessels; Blood Vessels - growth & development; Bone and Bones - blood supply; c-Kit protein; Cell Biology; Endocrinology; Endothelial cells; Life Sciences; Male; Mesenchyme; Mice; Original Research; Orthopedics; Osteoblasts; Parathyroid hormone; Parathyroid Hormone - administration & dosage; Parathyroid hormone-related protein; Proto-Oncogene Proteins c-kit - metabolism; Receptor, Parathyroid Hormone, Type 1 - metabolism; Stromal cells; Stromal Cells - cytology; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Vascular endothelial growth factor receptor 2; Vascular Endothelial Growth Factor Receptor-2 - metabolism
• ISSN: 0171-967X; 1432-0827
• DOI: 10.1007/s00223-020-00776-2

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.