Mg-Al and Zn-Al Layered Double Hydroxides Promote Dynamic Expression of Marker Genes in Osteogenic Differentiation by Modulating Mitogen-Activated Protein Kinases.
Ha Ram KangCélio Junior da Costa FernandesRodrigo Augusto da SilvaVera Regina Leopoldo ConstantinoIvan Hong Jun KohWillian Fernando ZambuzziPublished in: Advanced healthcare materials (2017)
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.
Keyphrases
- nuclear factor
- transcription factor
- bone loss
- bone regeneration
- signaling pathway
- genome wide identification
- toll like receptor
- bone mineral density
- genome wide
- drug delivery
- mesenchymal stem cells
- soft tissue
- bone marrow
- pi k akt
- heavy metals
- poor prognosis
- binding protein
- protein kinase
- bioinformatics analysis
- cell death
- oxidative stress
- ionic liquid
- cell proliferation
- immune response
- mass spectrometry
- copy number
- cancer therapy
- lps induced
- escherichia coli
- gene expression
- cystic fibrosis
- pseudomonas aeruginosa
- protein protein
- solar cells
- oxide nanoparticles