Open Access

Lack of endogenous parathyroid hormone delays fracture healing by inhibiting vascular endothelial growth factor‑mediated angiogenesis

  • Authors:
    • Qingfeng Ding
    • Peng Sun
    • Hao Zhou
    • Bowen Wan
    • Jian Yin
    • Yao Huang
    • Qingqing Li
    • Guoyong Yin
    • Jin Fan
  • View Affiliations

  • Published online on: April 3, 2018     https://doi.org/10.3892/ijmm.2018.3614
  • Pages: 171-181
  • Copyright: © Ding et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Intermittent low‑dose injections of parathyroid hormone (PTH) have been reported to exert bone anabolic effects and to promote fracture healing. As an important proangiogenic cytokine, vascular endothelial growth factor (VEGF) is secreted by bone marrow mesenchymal stem cells (BMSCs) and osteoblasts, and serves a crucial regulatory role in the process of vascular development and regeneration. To investigate whether lack of endogenous PTH causes reduced angiogenic capacity and thereby delays the process of fracture healing by downregulating the VEGF signaling pathway, a PTH knockout (PTHKO) mouse fracture model was generated. Fracture healing was observed using X‑ray and micro‑computerized tomography. Bone anabolic and angiogenic markers were analyzed by immunohistochemistry and western blot analysis. The expression levels of VEGF and associated signaling pathways in murine BMSC‑derived osteoblasts were measured by quantitative polymerase chain reaction and western blot analysis. The expression levels of protein kinase A (PKA), phosphorylated‑serine/threonine protein kinase (pAKT), hypoxia‑inducible factor‑1α (HIF1α) and VEGF were significantly decreased in BMSC‑derived osteoblasts from PTHKO mice. In addition, positive platelet endothelial cell adhesion molecule staining was reduced in PTHKO mice, as determined by immunohistochemistry. The expression levels of HIF1α, VEGF, runt‑related transcription factor 2, osteocalcin and alkaline phosphatase were also decreased in PTHKO mice, and fracture healing was delayed. In conclusion, lack of endogenous PTH may reduce VEGF expression in BMSC‑derived osteoblasts by downregulating the activity of the PKA/pAKT/HIF1α/VEGF pathway, thus affecting endochondral bone formation by causing a reduction in angiogenesis and osteogenesis, ultimately leading to delayed fracture healing.
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July-2018
Volume 42 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Ding Q, Sun P, Zhou H, Wan B, Yin J, Huang Y, Li Q, Yin G and Fan J: Lack of endogenous parathyroid hormone delays fracture healing by inhibiting vascular endothelial growth factor‑mediated angiogenesis. Int J Mol Med 42: 171-181, 2018
APA
Ding, Q., Sun, P., Zhou, H., Wan, B., Yin, J., Huang, Y. ... Fan, J. (2018). Lack of endogenous parathyroid hormone delays fracture healing by inhibiting vascular endothelial growth factor‑mediated angiogenesis. International Journal of Molecular Medicine, 42, 171-181. https://doi.org/10.3892/ijmm.2018.3614
MLA
Ding, Q., Sun, P., Zhou, H., Wan, B., Yin, J., Huang, Y., Li, Q., Yin, G., Fan, J."Lack of endogenous parathyroid hormone delays fracture healing by inhibiting vascular endothelial growth factor‑mediated angiogenesis". International Journal of Molecular Medicine 42.1 (2018): 171-181.
Chicago
Ding, Q., Sun, P., Zhou, H., Wan, B., Yin, J., Huang, Y., Li, Q., Yin, G., Fan, J."Lack of endogenous parathyroid hormone delays fracture healing by inhibiting vascular endothelial growth factor‑mediated angiogenesis". International Journal of Molecular Medicine 42, no. 1 (2018): 171-181. https://doi.org/10.3892/ijmm.2018.3614