Staphylococcus aureus internalization impairs osteoblastic activity and early differentiation process

Abstract Staphylococcus aureus is the most frequent aetiology of bone and joint infections (BJI) and can cause relapsing and chronic infections. One of the main factors involved in the chronicization of staphylococcal BJIs is the internalization of S. aureus into osteoblasts, the bone-forming cells....

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Autores principales:	W. Mouton, J. Josse, C. Jacqueline, L. Abad, S. Trouillet-Assant, J. Caillon, D. Bouvard, M. Bouchet, F. Laurent, A. Diot
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/50b5d0cbc9ed4069ac238978c2169b2e
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spelling	oai:doaj.org-article:50b5d0cbc9ed4069ac238978c2169b2e2021-12-02T16:37:37ZStaphylococcus aureus internalization impairs osteoblastic activity and early differentiation process10.1038/s41598-021-97246-y2045-2322https://doaj.org/article/50b5d0cbc9ed4069ac238978c2169b2e2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97246-yhttps://doaj.org/toc/2045-2322Abstract Staphylococcus aureus is the most frequent aetiology of bone and joint infections (BJI) and can cause relapsing and chronic infections. One of the main factors involved in the chronicization of staphylococcal BJIs is the internalization of S. aureus into osteoblasts, the bone-forming cells. Previous studies have shown that S. aureus triggers an impairment of osteoblasts function that could contribute to bone loss. However, these studies focused mainly on the extracellular effects of S. aureus. Our study aimed at understanding the intracellular effects of S. aureus on the early osteoblast differentiation process. In our in vitro model of osteoblast lineage infection, we first observed that internalized S. aureus 8325-4 (a reference lab strain) significantly impacted RUNX2 and COL1A1 expression compared to its non-internalized counterpart 8325-4∆fnbAB (with deletion of fnbA and fnbB). Then, in a murine model of osteomyelitis, we reported no significant effect for S. aureus 8325-4 and 8325-4∆fnbAB on bone parameters at 7 days post-infection whereas S. aureus 8325-4 significantly decreased trabecular bone thickness at 14 days post-infection compared to 8325-4∆fnbAB . When challenged with two clinical isogenic strains isolated from initial and relapse phase of the same BJI, significant impairments of bone parameters were observed for both initial and relapse strain, without differences between the two strains. Finally, in our in vitro osteoblast infection model, both clinical strains impacted alkaline phosphatase activity whereas the expression of bone differentiation genes was significantly decreased only after infection with the relapse strain. Globally, we highlighted that S. aureus internalization into osteoblasts is responsible for an impairment of the early differentiation in vitro and that S. aureus impaired bone parameters in vivo in a strain-dependent manner.W. MoutonJ. JosseC. JacquelineL. AbadS. Trouillet-AssantJ. CaillonD. BouvardM. BouchetF. LaurentA. DiotNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q W. Mouton J. Josse C. Jacqueline L. Abad S. Trouillet-Assant J. Caillon D. Bouvard M. Bouchet F. Laurent A. Diot Staphylococcus aureus internalization impairs osteoblastic activity and early differentiation process
description	Abstract Staphylococcus aureus is the most frequent aetiology of bone and joint infections (BJI) and can cause relapsing and chronic infections. One of the main factors involved in the chronicization of staphylococcal BJIs is the internalization of S. aureus into osteoblasts, the bone-forming cells. Previous studies have shown that S. aureus triggers an impairment of osteoblasts function that could contribute to bone loss. However, these studies focused mainly on the extracellular effects of S. aureus. Our study aimed at understanding the intracellular effects of S. aureus on the early osteoblast differentiation process. In our in vitro model of osteoblast lineage infection, we first observed that internalized S. aureus 8325-4 (a reference lab strain) significantly impacted RUNX2 and COL1A1 expression compared to its non-internalized counterpart 8325-4∆fnbAB (with deletion of fnbA and fnbB). Then, in a murine model of osteomyelitis, we reported no significant effect for S. aureus 8325-4 and 8325-4∆fnbAB on bone parameters at 7 days post-infection whereas S. aureus 8325-4 significantly decreased trabecular bone thickness at 14 days post-infection compared to 8325-4∆fnbAB . When challenged with two clinical isogenic strains isolated from initial and relapse phase of the same BJI, significant impairments of bone parameters were observed for both initial and relapse strain, without differences between the two strains. Finally, in our in vitro osteoblast infection model, both clinical strains impacted alkaline phosphatase activity whereas the expression of bone differentiation genes was significantly decreased only after infection with the relapse strain. Globally, we highlighted that S. aureus internalization into osteoblasts is responsible for an impairment of the early differentiation in vitro and that S. aureus impaired bone parameters in vivo in a strain-dependent manner.
format	article
author	W. Mouton J. Josse C. Jacqueline L. Abad S. Trouillet-Assant J. Caillon D. Bouvard M. Bouchet F. Laurent A. Diot
author_facet	W. Mouton J. Josse C. Jacqueline L. Abad S. Trouillet-Assant J. Caillon D. Bouvard M. Bouchet F. Laurent A. Diot
author_sort	W. Mouton
title	Staphylococcus aureus internalization impairs osteoblastic activity and early differentiation process
title_short	Staphylococcus aureus internalization impairs osteoblastic activity and early differentiation process
title_full	Staphylococcus aureus internalization impairs osteoblastic activity and early differentiation process
title_fullStr	Staphylococcus aureus internalization impairs osteoblastic activity and early differentiation process
title_full_unstemmed	Staphylococcus aureus internalization impairs osteoblastic activity and early differentiation process
title_sort	staphylococcus aureus internalization impairs osteoblastic activity and early differentiation process
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/50b5d0cbc9ed4069ac238978c2169b2e
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Staphylococcus aureus internalization impairs osteoblastic activity and early differentiation process

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