TY - JOUR
T1 - 3D cocultures of osteoblasts and staphylococcus aureus on biomimetic bone scaffolds as a tool to investigate the host–pathogen interface in osteomyelitis
AU - Parente, Raffaella
AU - Possetti, Valentina
AU - Schiavone, Maria Lucia
AU - Campodoni, Elisabetta
AU - Menale, Ciro
AU - Loppini, Mattia
AU - Doni, Andrea
AU - Bottazzi, Barbara
AU - Mantovani, Alberto
AU - Sandri, Monica
AU - Tampieri, Anna
AU - Sobacchi, Cristina
AU - Inforzato, Antonio
N1 - Funding Information:
This research was funded by Fondazione Beppe e Nuccy Angiolini. We would like to thank Fernando Gianfrancesco (CNR-IGB, Naples) for the kind gift of MC3T3 cell line.
Funding Information:
Funding: This research was funded by Fondazione Beppe e Nuccy Angiolini.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/7/3
Y1 - 2021/7/3
N2 - Osteomyelitis (OM) is an infectious disease of the bone primarily caused by the opportunistic pathogen Staphylococcus aureus (SA). This Gram-positive bacterium has evolved a number of strategies to evade the immune response and subvert bone homeostasis, yet the underlying mechanisms remain poorly understood. OM has been modeled in vitro to challenge pathogenetic hypotheses in controlled conditions, thus providing guidance and support to animal experimentation. In this regard, traditional 2D models of OM inherently lack the spatial complexity of bone architecture. Three-dimensional models of the disease overcome this limitation; however, they poorly reproduce composition and texture of the natural bone. Here, we developed a new 3D model of OM based on cocultures of SA and murine osteoblastic MC3T3-E1 cells on magnesium-doped hydroxyapatite/collagen I (MgHA/Col) scaffolds that closely recapitulate the bone extracellular matrix. In this model, matrix-dependent effects were observed in proliferation, gene transcription, protein expression, and cell–matrix interactions both of the osteoblastic cell line and of bacterium. Additionally, these had distinct metabolic and gene expression profiles, compared to conventional 2D settings, when grown on MgHA/Col scaffolds in separate monocultures. Our study points to MgHA/Col scaffolds as biocompatible and bioactive matrices and provides a novel and close-to-physiology tool to address the pathogenetic mechanisms of OM at the host–pathogen interface.
AB - Osteomyelitis (OM) is an infectious disease of the bone primarily caused by the opportunistic pathogen Staphylococcus aureus (SA). This Gram-positive bacterium has evolved a number of strategies to evade the immune response and subvert bone homeostasis, yet the underlying mechanisms remain poorly understood. OM has been modeled in vitro to challenge pathogenetic hypotheses in controlled conditions, thus providing guidance and support to animal experimentation. In this regard, traditional 2D models of OM inherently lack the spatial complexity of bone architecture. Three-dimensional models of the disease overcome this limitation; however, they poorly reproduce composition and texture of the natural bone. Here, we developed a new 3D model of OM based on cocultures of SA and murine osteoblastic MC3T3-E1 cells on magnesium-doped hydroxyapatite/collagen I (MgHA/Col) scaffolds that closely recapitulate the bone extracellular matrix. In this model, matrix-dependent effects were observed in proliferation, gene transcription, protein expression, and cell–matrix interactions both of the osteoblastic cell line and of bacterium. Additionally, these had distinct metabolic and gene expression profiles, compared to conventional 2D settings, when grown on MgHA/Col scaffolds in separate monocultures. Our study points to MgHA/Col scaffolds as biocompatible and bioactive matrices and provides a novel and close-to-physiology tool to address the pathogenetic mechanisms of OM at the host–pathogen interface.
KW - 3D models
KW - Biomimetic bone scaffolds
KW - Host–pathogen interface
KW - Osteoblast-like cells
KW - Osteomyelitis
KW - Staphylococcus aureus
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U2 - 10.3390/pathogens10070837
DO - 10.3390/pathogens10070837
M3 - Article
C2 - 34357987
AN - SCOPUS:85110412747
SN - 2076-0817
VL - 10
JO - Pathogens
JF - Pathogens
IS - 7
M1 - 837
ER -