Mg-Al and Zn-Al Layered Double Hydroxides Promote Dynamic Expression of Marker Genes in Osteogenic Differentiation by Modulating Mitogen-Activated Protein Kinases

Adv Healthc Mater. 2018 Feb;7(4). doi: 10.1002/adhm.201700693. Epub 2017 Dec 27.

Abstract

The effect of LDH samples comprised of chloride anions intercalated between positive layers of magnesium/aluminum (Mg-Al LDH) or zinc/aluminum (Zn-Al LDH) chemical composition on pre-osteoblast performance is investigated. Non-cytotoxic concentrations of both LDHs modulated pre-osteoblast adhesion by triggering cytoskeleton rearrangement dependent on recruiting of Cofilin, which is modulated by the inhibition of the Protein Phosphatase 2A (PP2A), culminating in osteoblast differentiation with a significant increase of osteogenic marker genes. The alkaline phosphatase (ALP) and bone sialoprotein (BSP) are significantly up-modulated by both LDHs; however, Mg-Al LDH nanomaterial promoted even more significance than both experimental controls, while the phosphorylations of mitogen-activated protein kinase (MAPKs)- extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinase (JNK) significantly increased. MAPK signaling is necessary to activate Runt-related transcription factor 2 (RUNX2) gene. Concomitantly, it is also investigated whether challenged osteoblasts are able to modulate osteoclastogenesis by investigating both osteoprotegerin (OPG) and Receptor activator of nuclear factor kappa-ligand (RANKL) in this model; a dynamic reprogramming of both these genes is found, suggesting LDHs in modulating osteoclastogenesis. These results suggest that LDHs interfere in bone remodeling, and they can be considered as nanomaterials in graft-based bone healing or drug-delivery materials for bone disorders.

Keywords: differentiation; double metal hydroxides; hydrotalcite-like materials; layered double hydroxides; nanoparticles; osteoblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aluminum / chemistry
  • Animals
  • Bone Substitutes / chemistry*
  • Bone Substitutes / pharmacology
  • Cell Adhesion / drug effects
  • Cell Differentiation* / drug effects
  • Cell Line
  • Extracellular Matrix / metabolism
  • Hydroxides / chemistry*
  • Magnesium / chemistry
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteogenesis* / drug effects
  • Osteopontin / genetics
  • Osteopontin / metabolism
  • RANK Ligand / metabolism
  • Up-Regulation / drug effects
  • Zinc / chemistry

Substances

  • Bone Substitutes
  • Hydroxides
  • RANK Ligand
  • Osteopontin
  • Aluminum
  • Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinases
  • Magnesium
  • Zinc