| First Author | Ding Q | Year | 2018 |
| Journal | Int J Mol Med | Volume | 42 |
| Issue | 1 | Pages | 171-181 |
| PubMed ID | 29620150 | Mgi Jnum | J:277597 |
| Mgi Id | MGI:6282064 | Doi | 10.3892/ijmm.2018.3614 |
| Citation | Ding Q, et al. (2018) Lack of endogenous parathyroid hormone delays fracture healing by inhibiting vascular endothelial growth factormediated angiogenesis. Int J Mol Med 42(1):171-181 |
| abstractText | Intermittent lowdose 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 Xray and microcomputerized 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 BMSCderived osteoblasts were measured by quantitative polymerase chain reaction and western blot analysis. The expression levels of protein kinase A (PKA), phosphorylatedserine/threonine protein kinase (pAKT), hypoxiainducible factor1alpha (HIF1alpha) and VEGF were significantly decreased in BMSCderived 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 HIF1alpha, VEGF, runtrelated 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 BMSCderived osteoblasts by downregulating the activity of the PKA/pAKT/HIF1alpha/VEGF pathway, thus affecting endochondral bone formation by causing a reduction in angiogenesis and osteogenesis, ultimately leading to delayed fracture healing. |
