Impact of Bone Morphogenetic Protein 7 and Prostaglandin receptors on osteoblast healing and organization of collagen

PLoS One. 2024 May 16;19(5):e0303202. doi: 10.1371/journal.pone.0303202. eCollection 2024.

Abstract

Purpose: This study seeks to investigate the impact of co-administering either a Prostaglandin EP2 receptor agonist or an EP1 receptor antagonist alone with a low dose BMP7 on in vitro healing process, collagen content and maturation of human osteoblasts.

Methodology: Human osteoblast cells were used in this study. These cells were cultured and subjected to different concentrations of Prostaglandin EP2 receptor agonist, EP1 receptor antagonist, BMP7, Control (Ct) (Vehicle alone), and various combinations treatments. Cell viability at 24, 48 and 72 hours (h) was evaluated using the XTT assay. A wound healing assay was conducted to observe the migration ability of human osteoblast cells. Additionally, Sirius red staining and Fourier-Transform Infrared Spectroscopy Imaging (FT-IR) was employed to analyze various parameters, including total protein concentration, collagen production, mature collagen concentration, and mineral content.

Results: The combination of low dose BMP7 and Prostaglandin EP2 receptor agonist resulted to the lowest cell viability when compared to both the Ct and individual treatments. In contrast, the Prostaglandin EP1 receptor antagonist alone showed the highest cellular viability at 72 h. In the wound healing assay, the combined treatment of low dose BMP7 with the Prostaglandin EP2 receptor agonist and EP1 receptor antagonist showed a decrease in human osteoblast healing after 24 h. Analysis of FT-IR data indicated a reduction in total protein content, collagen maturity, collagen concentration and mineral content in combination treatment compared to the single or Ct treatments.

Conclusion: The combination of a Prostaglandin EP2 receptor agonist or an EP1 receptor antagonist when combined with low dose BMP7 significantly hinders both human osteoblast healing and collagen maturity/concentration in comparison to low dose BMP7 treatment alone.

MeSH terms

  • Bone Morphogenetic Protein 7* / pharmacology
  • Cell Line
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Collagen* / metabolism
  • Humans
  • Osteoblasts* / drug effects
  • Osteoblasts* / metabolism
  • Receptors, Prostaglandin E, EP1 Subtype / metabolism
  • Receptors, Prostaglandin E, EP2 Subtype* / agonists
  • Receptors, Prostaglandin E, EP2 Subtype* / metabolism
  • Spectroscopy, Fourier Transform Infrared*
  • Wound Healing / drug effects

Substances

  • BMP7 protein, human
  • Bone Morphogenetic Protein 7
  • Collagen
  • Receptors, Prostaglandin E, EP1 Subtype
  • Receptors, Prostaglandin E, EP2 Subtype

Grants and funding

Vice Chancellor for Research and Graduate Studies & Research Institute for Medical and Health sciences at the University of Sharjah. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."