Expression of Musashi-1 Increases in Bone Healing

Int J Mol Sci. 2021 Mar 26;22(7):3395. doi: 10.3390/ijms22073395.

Abstract

Musashi-1 (MSI1) is an RNA-binding protein that regulates progenitor cells in adult and developing organisms to maintain self-renewal capacities. The role of musashi-1 in the bone healing environment and its relation with other osteogenic factors is unknown. In the current study, we analyze the expression of MSI1 in an experimental model of rat femoral bone fractures. We also analyze the relation between MSI1 expression and the expression of two osteogenic markers: periostin (POSTN) and runt-related transcription factor 2 (RUNX2). We use histological, immunohistochemical, and qPCR techniques to evaluate bone healing and the expression of MSI1, POSTN, and RUNX2 over time (4, 7, and 14 days). We compare our findings with non-fractured controls. We find that in bone calluses, the number of cells expressing MSI1 and RUNX2 increase over time and the intensity of POSTN expression decreases over time. Within bone calluses, we find the presence of MSI1 expression in mesenchymal stromal cells, osteoblasts, and osteocytes but not in hypertrophic chondrocytes. After 14 days, the expression of MSI1, POSTN, and RUNX2 was significantly correlated. Thus, we conclude that musashi-1 potentially serves in the osteogenic differentiation of mesenchymal stromal cells and bone healing. Therefore, further studies are needed to determine the possibility of musashi-1's role as a clinical biomarker of bone healing and therapeutic agent for bone regeneration.

Keywords: Musashi-1; Runx2; bone healing; mesenchymal stem cells; periostin.

MeSH terms

  • Animals
  • Bony Callus / cytology
  • Bony Callus / metabolism
  • Bony Callus / physiology
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Chondrocytes / metabolism
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Fracture Healing*
  • Male
  • Mesenchymal Stem Cells / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Osteoblasts / metabolism
  • Osteocytes / metabolism
  • Osteogenesis*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Rats
  • Rats, Wistar

Substances

  • Cell Adhesion Molecules
  • Core Binding Factor Alpha 1 Subunit
  • Msi1 protein, rat
  • Nerve Tissue Proteins
  • Postn protein, rat
  • RNA-Binding Proteins
  • Runx2 protein, rat