Differential inflammatory landscape stimulus during titanium surfaces obtained osteogenic phenotype

Author(s)

Feltran, Georgia da S. ^[1] ; Bezerra, Fabio ^[1] ; da Costa Fernandes, Celio Junior ^[1] ; Ferreira, Marcel Rodrigues ^[1] ; Zambuzzi, Willian F. ^{[1, 2]}

Affiliation

^[1] State Univ Sao Paulo UNESP, Biosci Inst, Dept Chem & Biochem, Campus Botucatu, Botucatu, SP - Brazil

^[2] UNESP, IBB, Electron Microscopy Ctr, Botucatu, SP - Brazil

• Document type: Journal article
• Source: Journal of Biomedical Materials Research Part A; v. 107, n. 8, p. 1597-1604, AUG 2019.
• Web of Science Citations: 1

Abstract

Molecular mechanism governing inflammatory scenario in response to titanium (Ti)-nanotexturing surfaces needs to be better addressed. Thus, we subjected pre-osteoblast to different Ti-texturing surfaces, as follows: machined (Mac), double acid-etching (DAE), and nanoscaled hydroxyapatite-blasted titanium surface (nHA), considering the cells chronically responding either directly (when the cells were cultured onto the surfaces) or indirectly (when the cells were challenged with the conditioned medium by the surfaces), up to 10 days. Our results showed that there is a dynamic requirement of inflammatory-related genes activation in response to nHA by up expressing IL1 ss, IL6, IL10, and IL33 (direct condition) and IL6, IL10, IL18 (indirect condition). Importantly, our data show that there is inflammasome involvement, once NLRP3, ASC1, and CASP1 genes were also required. As we found a strong signal of IL10, an anti-inflammatory cytokine, we further investigated Sonic Hedgehog (Shh) signaling cascade. Surprisingly, Shh ligand and Smoothened (Smo) genes were up-modulated in response to nHA, while Patched (Ptc) was down-modulated. Finally, an interactome was built using bioinformatics reinforcing Shh signaling cascade on modulating IL10 transcripts by Src mediating this process and this prevalence of anti-inflammatory picture might explain the low profile of RANKL transcripts in response to nHA, compromising the osteoclastogenesis surrounding the implants. Taking our results into account, our data show that the inflammatory landscape promoted by nHA is strictly modulated by Shh signaling promoted anti-inflammatory pathways. (c) 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1597-1604, 2019. (AU)

• 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