Strontium-Substituted Bioceramics Particles: A New Way to Modulate MCP-1 and Gro-α Production by Human Primary Osteoblastic Cells.

Julien Braux,Patrice Laquerrière,Edouard Jallot,Frédéric Velard,Christine Guillaume,Marie-Laure Jourdain,Jean-Marie Nedelec,Sophie Gangloff,Dominique Laurent-Maquin

doi:10.3390/ma9120985

Abstract

Background: To avoid morbidity and limited availability associated with autografts, synthetic calcium phosphate (CaP) ceramics were extensively developed and used as bone filling materials. Controlling their induced-inflammatory response nevertheless remained a major concern. Strontium-containing CaP ceramics were recently demonstrated for impacting cytokines’ secretion pattern of human primary monocytes. The present study focuses on the ability of strontium-containing CaP to control the human primary bone cell production of two major inflammatory and pro-osteoclastogenic mediators, namely MCP-1 and Gro-α, in response to ceramics particles. Methods: This in vitro study was performed using human primary osteoblasts in which their response to ceramics was evaluated by PCR arrays, antibody arrays were used for screening and real-time PCR and ELISA for more focused analyses. Results: Study of mRNA and protein expression highlights that human primary bone cells are able to produce these inflammatory mediators and reveal that the adjunction of CaP in the culture medium leads to their enhanced production. Importantly, the current work determines the down-regulating effect of strontium-substituted CaP on MCP-1 and Gro-α production. Conclusion: Our findings point out a new capability of strontium to modulate human primary bone cells’ communication with the immune system.

Highlights

Despite much research in the biomaterial field, the gold standard technique to treat large bone defects still consists of autologous bone grafts
This study is the first to evaluate the effect of strontium—especially of Biphasic Calcium Phosphate (BCP) containing strontium—on CCL2/MCP-1 and CXCL1/Gro-α expression and production by human primary bone cells
Among pro-inflammatory factors acting on bones, tumor necrosis factor α (TNF-α), IL-6, IL-1β, and the receptor activator of nuclear factor (NF)-κB (RANK)/RANK ligand (RANKL)/osteoprotegrin (OPG) triad [22,35] have been largely described for their tight regulation of mechanisms that govern osteoclast development and activity

Summary

Introduction

Despite much research in the biomaterial field, the gold standard technique to treat large bone defects still consists of autologous bone grafts. Synthetic calcium phosphate (CaP) ceramics are widely used as bone filling materials as a substitute to auto/allograft thanks to their similarity with the inorganic phase of bone and their osteoconductive properties Despite their good biocompatibility and their ability to increase the integration of coated implants [2,3,4], CaP materials demonstrate feeble bone cell stimulation and have a tendency to fragment and generate particles which are known to provoke a pro-inflammatory response, which could be harmful and affect long term implant survival [5,6,7,8]. To avoid morbidity and limited availability associated with autografts, synthetic calcium phosphate (CaP) ceramics were extensively developed and used as bone filling materials Controlling their induced-inflammatory response remained a major concern. The present study focuses on the ability of strontium-containing CaP to control the human primary bone cell production of two major inflammatory and pro-osteoclastogenic mediators, namely MCP-1 and Gro-α, in response to ceramics particles. Conclusion: Our findings point out a new capability of strontium to modulate human primary bone cells’ communication with the immune system

Methods

Results

Conclusion