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Involvement of FAK-Mediated BMP-2/Smad Pathway in Mediating Osteoblast Adhesion and Differentiation on Nano-Hydroxyapatite/ Chitosan Composite Coated Titanium Implant under Diabetes

Abstract

Chitosan (CS)-based hydroxyapatite (HA) composite emerges as a novel strategy for promoting bone regeneration. Here the nanophase HA/CS composite coated porous titanium implant (nCT) was fabricated and its biological behavior under diabetic conditions was investigated. We proposed that focal adhesion kinase (FAK)-mediated BMP-2/Smad pathway played a role in mediating the promotive effect of nCT on osteoblast adhesion and differentiation under diabetes-induced high reactive oxygen species (ROS) condition. To confirm the hypothesis, rat osteoblasts on bare titanium implant (Ti) and nCT were subjected to normal serum (NS), diabetic serum (DS), DS + NAC (a potent ROS inhibitor) and DS + cytochalasin D (an actin polymerization inhibitor). In vivo study was performed on diabetic sheep implanted with Ti or nCT. Results showed that diabetes-induced ROS overproduction impaired osteoblast adhesion evidenced by immunostaining of F-actin and vinculin, and morphological observation through inhibition of FAK phosphorylation, which contributed to suppressed BMP-2-dependent Smad1/5/8 phosphorylation. nCT substrate reactivated FAK-BMP-2/Smad pathway, thus reversed osteoblast dysfunctions, which exerted similar effect to NAC treatment on Ti. These effects were further confirmed by the improved osteointegration within nCT in diabetic sheep evidenced by micro-CT and histological examinations. Our study demonstrated reactivation of FAK-BMP-2/Smad pathway was involved in improving osteoblast adhesion and differentiation by nano-HA/CS composite coating, hopefully directing biomaterial modification and biofunctionalization under diabetic conditions.

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Publication details

The article was received on 22 Jul 2017, accepted on 06 Nov 2017 and first published on 07 Nov 2017


Article type: Paper
DOI: 10.1039/C7BM00652G
Citation: Biomater. Sci., 2017, Accepted Manuscript
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    Involvement of FAK-Mediated BMP-2/Smad Pathway in Mediating Osteoblast Adhesion and Differentiation on Nano-Hydroxyapatite/ Chitosan Composite Coated Titanium Implant under Diabetes

    X. Ma, Y. Feng, T. Wang, W. Lei, X. Li, D. Zhou, X. Wen, H. Yu, L. Xiang and L. Wang, Biomater. Sci., 2017, Accepted Manuscript , DOI: 10.1039/C7BM00652G

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