The Crosstalk between Osteoclasts and Osteoblasts Is Dependent upon the Composition and Structure of Biphasic Calcium Phosphates

Yukari Shiwaku,Lynn Neff,Kenichi Nagano,Roland Baron,Ken-Ichi Takeyama,Joost De Bruijn,Michel Dard,Francesca Gori,Luc Malaval

doi:10.1371/journal.pone.0132903

Abstract

Biphasic calcium phosphates (BCPs), consisting of hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), exhibit good biocompatibility and osteoconductivity, maintaining a balance between resorption of the biomaterial and formation of new bone. We tested whether the chemical composition and/or the microstructure of BCPs affect osteoclasts (OCs) differentiation and/or their ability to crosstalk with osteoblasts (OBs). To this aim, OCs were cultured on BCPs with HA content of 5, 20 or 60% and their differentiation and activity were assessed. We found that OC differentiation is partially impaired by increased HA content, but not by the presence of micropores within BCP scaffolds, as indicated by TRAP staining and gene profile expression. We then investigated whether the biomaterial-induced changes in OC differentiation also affect their ability to crosstalk with OBs and regulate OB function. We found that BCPs with low percentage of HA favored the expression of positive coupling factors, including sphingosine-kinase 1 (SPHK1) and collagen triple helix repeat containing 1 (Cthrc1). In turn, the increase of these secreted coupling factors promotes OB differentiation and function. All together our studies suggest that the chemical composition of biomaterials affects not only the differentiation and activity of OCs but also their potential to locally regulate bone formation.

Highlights

Synthetic biomaterials are routinely used as bone substitutes in orthopedic surgery to repair large bone defects caused by tumors or trauma [1,2] and in oral surgery for alveolar ridgePLOS ONE | DOI:10.1371/journal.pone.0132903 July 20, 2015Osteoclast-Osteoblast Crosstalk on Biphasic calcium phosphates (BCPs) augmentation and treatment of infrabony periodontal defects [3]
The chemical composition of BCPs was characterized by X-ray diffraction (XRD) (Fig 1)
We examined the surface topography of each BCP using Field Emission Scanning Electron Microscope (FE-SEM) (Fig 2). 5HA dense and 5HA porous have small and fine crystals, 2~10 μm or 0.5~2 μm in length, respectively

Summary

Introduction

Synthetic biomaterials are routinely used as bone substitutes in orthopedic surgery to repair large bone defects caused by tumors or trauma [1,2] and in oral surgery for alveolar ridgePLOS ONE | DOI:10.1371/journal.pone.0132903 July 20, 2015Osteoclast-Osteoblast Crosstalk on BCPs augmentation and treatment of infrabony periodontal defects [3]. Autografts still remain the gold standard for bone repair, substitution and augmentation followed by allografts, but both have major drawbacks that include limited availability, morbidity associated with the donor site, and potential transmission of pathogens in the case of allografts [4]. The rationale behind the use of calcium phosphate (CaP) materials as bone substitutes is that their composition is similar to that of the mineral phase of bone, including some key properties of bone, such as biodegradability, bioactivity and osteoconductivity [1,5]. CaP materials are classified based on their composition as: hydroxyapatite (HA), Ca10(PO4)6(OH); beta-tricalcium phosphate (β -TCP), Ca3(PO4) and biphasic calcium phosphate (BCP), an intimate mixture of HA and β-TCP of varying HA/β-TCP weight ratio. The composition of the CaP material has direct consequences on its performance, including its ability to be resorbed by osteoclasts (OCs) [6]. OC differentiation and activity are affected by the other physicochemical properties of CaPs, such as surface roughness, surface topography and crystallinity. [10,11,12,13,14]

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