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

Author(s)

Kang, Ha Ram ^[1] ; da Costa Fernandes, Celio Junior ^[1] ; da Silva, Rodrigo Augusto ^[1] ; Leopoldo Constantino, Vera Regina ^[2] ; Jun Koh, Ivan Hong ^[3] ; Zambuzzi, Willian F. ^[1]

Affiliation

^[1] Univ Estadual Paulista, UNESP, Lab Bioensaios & Dinam Celular, Dept Quim & Bioquim, Inst Biociencias, Campus Botucatu, BR-18618970 Sao Paulo - Brazil

^[2] Univ Sao Paulo, USP, Inst Quim, Dept Quim Fundamental, Av Prof Lineu Prestes 748, BR-05508000 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, UNIFESP, Dept Cirurgia, Rua Botucatu 740, BR-04023900 Sao Paulo - Brazil

• Document type: Journal article
• Source: ADVANCED HEALTHCARE MATERIALS; v. 7, n. 4 FEB 21 2018.
• Web of Science Citations: 8

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. (AU)

• FAPESP's process: 11/50318-1 - Development of compounds with pharmacological or medicinal interest and of systems for their transport, detection and recognition in biological media
• Grantee: Ana Maria da Costa Ferreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/22689-3 - Microvesicle/proteins-mediated paracrine signaling among bone and endothelial cells during bone development and regeneration
• Grantee: Willian Fernando Zambuzzi
• Support Opportunities: Research Grants - Young Investigators Grants