PTH promotes rabbit tibial fracture healing via the Notch signaling pathway

Eur Rev Med Pharmacol Sci. 2020 Feb;24(4):1616-1623. doi: 10.26355/eurrev_202002_20336.

Abstract

Objective: To explore the effect of parathyroid hormone (PTH) on the expression of Jagged1 in the rabbit tibial fracture healing, and its function and mechanism in this process via the Notch signaling pathway.

Materials and methods: A total of 60 New Zealand white rabbits were randomly divided into control group (n=30) and experimental group (n=30). Then, a rabbit tibial fracture model was established. After surgery, the rabbits in experimental group were given 10 μg/kg PTH (1-34) once a day for 5 days a week, while those in control group were given an equal volume of normal saline. Six rabbits were randomly selected from each group at 1, 2, 3, 4, and 6 weeks after surgery to collect right tibia specimens. Next, X-ray examination, bone mineral density (BMD) test, histological detection, and serum biochemical test were performed. Additionally, the messenger ribonucleic acid (mRNA) expression levels of Notch1 and Jagged1 in the Notch signaling pathway were measured via polymerase chain reaction (PCR) assay. Their protein levels were detected through Western blotting analysis.

Results: The healing and BMD in experimental group were better than those in control group since cortical and medullary bridging was observed in the rabbits of experimental group at the 6th week after surgery. Plasma level of alkaline phosphatase (ALP), P content, and the product of Ca and P significantly increased (p<0.05) in experimental group. The pathological morphology of the calluses stained with hematoxylin-eosin (HE) in experimental group was overtly superior to that in control group. The PCR results revealed that both mRNA and protein levels of Notch1 and Jagged1 were lower in control group than those in experimental group (p<0.05).

Conclusions: PTH (1-34) promotes the rabbit tibial fracture healing by regulating Jagged1 ligand molecules in the Notch signaling pathway.

MeSH terms

  • Animals
  • Fracture Healing / drug effects*
  • Jagged-1 Protein / genetics
  • Jagged-1 Protein / metabolism*
  • Parathyroid Hormone / pharmacology*
  • Rabbits
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Signal Transduction / drug effects
  • Tibia / drug effects
  • Tibia / metabolism
  • Tibia / pathology
  • Tibial Fractures / genetics
  • Tibial Fractures / metabolism*
  • Tibial Fractures / pathology

Substances

  • Jagged-1 Protein
  • Parathyroid Hormone
  • Receptors, Notch