tBHQ Suppresses Osteoclastic Resorption in Xenogeneic-Treated Dentin Matrix-Based Scaffolds

Adv Healthc Mater. 2017 Sep;6(18). doi: 10.1002/adhm.201700127. Epub 2017 Jul 11.

Abstract

Extracellularmatrix (ECM)-based scaffolds are important for their potential therapeutic application. Treated dentin matrix (TDM), a kind of ECM, seeded with allogeneic dental follicle stem cells (TDM/aDFC) provides a suitable inductive microenvironment for tooth root regeneration. Considering the limited sources, xenogeneic TDM (xTDM) is a possible alternative to allogeneic TDM; however, xTDM-based scaffold presents severe osteolysis and resorption lacunae causing regenerated tooth root failure. Immune response-induced excessive osteoclastogenesis plays a critical role in xenogeneic scaffold osteolysis and resorption. The impact of antioxidant, tert-butylhydroquinone (tBHQ), on xTDM/aDFCs-induced osteoclastogenesis and osteoclastic resorption in vivo and in vitro are investigated. tBHQ upregulates heme oxygenase-1 release and downregulates high mobility group box 1 mRNA expression. mRNA expression of other osteoclast-related genes including nuclear factor-kappa Bp65, receptor activator of nuclear factor kappa-B, nuclear factor of activated T-cells cytoplasmic 1, cathepsin K, and integrin β3, also decreases significantly. Furthermore, tBHQ-treated xTDM/aDFCs scaffolds implanted into rhesus macaques show reduced osteolysis and osteoclastic resorption by microcomputed tomography and tartrate-resistant acid phosphatase staining. tBHQ-induced suppression of xTDM/aDFC-induced osteoclastogenesis and osteoclastic resorption presents a new strategy for the regeneration of biological tooth root and could be applied to the regeneration of other complex tissues and organs.

Keywords: extracellular matrix (ECM); osteoclastic resorption; tert-butylhydroquinone (tBHQ); treated dentin matrix (TDM)-based scaffolds.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Dental Sac / drug effects
  • Dental Sac / metabolism
  • Dentin / metabolism*
  • Down-Regulation / drug effects
  • HMGB Proteins / metabolism
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Hydroquinones / pharmacology*
  • Macaca mulatta
  • Male
  • Osteoclasts / drug effects*
  • Osteoclasts / metabolism
  • Osteogenesis / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Regeneration / drug effects
  • Stem Cells / drug effects
  • Tissue Scaffolds
  • Tooth Root / drug effects
  • Tooth Root / metabolism
  • Up-Regulation / drug effects

Substances

  • HMGB Proteins
  • Hydroquinones
  • 2-tert-butylhydroquinone
  • Heme Oxygenase-1