Sonic Hedgehog Regulates Bone Fracture Healing

Int J Mol Sci. 2020 Jan 20;21(2):677. doi: 10.3390/ijms21020677.

Abstract

Bone fracture healing involves the combination of intramembranous and endochondral ossification. It is known that Indian hedgehog (Ihh) promotes chondrogenesis during fracture healing. Meanwhile, Sonic hedgehog (Shh), which is involved in ontogeny, has been reported to be involved in fracture healing, but the details had not been clarified. In this study, we demonstrated that Shh participated in fracture healing. Six-week-old Sprague-Dawley rats and Gli-CreERT2; tdTomato mice were used in this study. The right rib bones of experimental animals were fractured. The localization of Shh and Gli1 during fracture healing was examined. The localization of Gli1 progeny cells and osterix (Osx)-positive cells was similar during fracture healing. Runt-related transcription factor 2 (Runx2) and Osx, both of which are osteoblast markers, were observed on the surface of the new bone matrix and chondrocytes on day seven after fracture. Shh and Gli1 were co-localized with Runx2 and Osx. These findings suggest that Shh is involved in intramembranous and endochondral ossification during fracture healing.

Keywords: animal experiment; fracture healing; sonic hedgehog; stem cell.

MeSH terms

  • Animals
  • Bone and Bones / physiology
  • Cell Differentiation
  • Chondrocytes / physiology
  • Chondrogenesis / physiology*
  • Fracture Healing / physiology*
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Immunohistochemistry
  • Male
  • Mice
  • Osteoblasts / physiology
  • Osteogenesis / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Smoothened Receptor / genetics
  • Smoothened Receptor / metabolism
  • Zinc Finger Protein GLI1 / genetics
  • Zinc Finger Protein GLI1 / metabolism

Substances

  • Gli1 protein, mouse
  • Gli1 protein, rat
  • Hedgehog Proteins
  • Shh protein, mouse
  • Shh protein, rat
  • Smo protein, mouse
  • Smo protein, rat
  • Smoothened Receptor
  • Zinc Finger Protein GLI1