Platelet-derived biomaterials-mediated improvement of bone injury through migratory ability of embryonic fibroblasts: in vitro and in vivo evidence

Aging (Albany NY). 2021 Jan 10;13(3):3605-3617. doi: 10.18632/aging.202311. Epub 2021 Jan 10.

Abstract

Bony injuries lead to compromised skeletal functional ability which further increase in aging population due to decreased bone mineral density. Therefore, we aimed to investigate the therapeutic potential of platelet-derived biomaterials (PDB) against bone injury. Specifically, we assessed the impact of PDB on osteo-inductive characteristics and migration of mouse embryonic fibroblasts (MEFs). Osteogenic lineage, matrix mineralization and cell migration were determined by gene markers (RUNX2, OPN and OCN), alizarin Red S staining, and migration markers (FAK, pFAK and Src) and EMT markers, respectively. The therapeutic impact of TGF-β1, a key component of PDB, was confirmed by employing inhibitor of TGF-β receptor I (Ti). Molecular imaging-based in vivo cellular migration in mice was determined by establishing bone injury at right femurs. Results showed that PDB markedly increased expression of osteogenic markers, matrix mineralization, migration and EMT markers, revealing higher osteogenic and migratory potential of PDB-treated MEFs. In vivo cell migration was manifested by expression of migratory factors, SDF-1 and CXCR4. Compared to control, PDB-treated mice exhibited higher bone density and volume. Ti treatment inhibited both migration and osteogenic potential of MEFs, affirming impact of TGF-β1. Collectively, our study clearly indicated PDB-rescued bone injury through enhancing migratory potential of MEFs and osteogenesis.

Keywords: TGF-β1; bone injury; fibroblasts migration; osteogenesis; platelet-derived biomaterials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials*
  • Blood Platelets / metabolism*
  • Bone Density
  • Bone Regeneration*
  • Calcification, Physiologic
  • Cell Lineage
  • Cell Movement*
  • Chemokine CXCL12
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Epithelial-Mesenchymal Transition
  • Femur / injuries*
  • Femur / metabolism
  • Femur / pathology
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Focal Adhesion Kinase 1
  • In Vitro Techniques
  • Mice
  • NIH 3T3 Cells
  • Osteocalcin / genetics
  • Osteogenesis*
  • Osteopontin / genetics
  • Receptors, CXCR4
  • Transforming Growth Factor beta1 / antagonists & inhibitors
  • Transforming Growth Factor beta1 / metabolism*
  • src-Family Kinases

Substances

  • Biocompatible Materials
  • CXCR4 protein, mouse
  • Chemokine CXCL12
  • Core Binding Factor Alpha 1 Subunit
  • Cxcl12 protein, mouse
  • Receptors, CXCR4
  • Runx2 protein, mouse
  • Spp1 protein, mouse
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta1
  • Osteocalcin
  • Osteopontin
  • Focal Adhesion Kinase 1
  • Ptk2 protein, mouse
  • src-Family Kinases