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Published on: September 8, 2021
Staphylococcus aureus internalization impairs osteoblastic activity and early differentiation process
W Mouton1,2, J Josse3,4, C Jacqueline5
1CIRI - Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon, Université Lyon, Lyon, France.
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.
Insights
Staphylococcus aureus internalization into bone cells impairs early differentiation. This bacterial invasion causes bone loss in a strain-dependent manner, impacting chronic bone and joint infections.
Area of Science:
- Microbiology
- Orthopedics
- Cell Biology
Background:
- Staphylococcus aureus is a primary cause of bone and joint infections (BJIs), often leading to chronic or relapsing conditions.
- Bacterial internalization into osteoblasts is a key factor in staphylococcal BJI chronicity and associated bone loss.
- Previous research focused on extracellular bacterial effects, necessitating investigation into intracellular impacts on osteoblasts.
Purpose of the Study:
- To elucidate the intracellular effects of Staphylococcus aureus on early osteoblast differentiation.
- To determine the role of bacterial internalization in osteoblast dysfunction and bone parameter changes.
- To compare the effects of reference and clinical strains of S. aureus on bone health.
Main Methods:
- In vitro infection model using osteoblast lineage cells and S. aureus strains (8325-4 and 8325-4∆fnbAB).
- Murine model of osteomyelitis to assess bone parameters (trabecular bone thickness) at 7 and 14 days post-infection.
- Infection with clinical isogenic strains from initial and relapse BJI phases to evaluate their impact on osteoblast differentiation markers and bone parameters.
Main Results:
- Internalized S. aureus 8325-4 significantly affected RUNX2 and COL1A1 gene expression in vitro compared to non-internalized bacteria.
- In vivo, S. aureus 8325-4 reduced trabecular bone thickness at 14 days post-infection, while 8325-4∆fnbAB showed no significant effect.
- Both clinical strains impaired bone parameters in vivo; in vitro, they affected alkaline phosphatase activity, with the relapse strain further decreasing bone differentiation gene expression.
Conclusions:
- Staphylococcus aureus internalization into osteoblasts impairs early osteoblast differentiation in vitro.
- S. aureus infection leads to impaired bone parameters in vivo in a strain-dependent manner.
- Bacterial internalization is a critical mechanism driving osteoblast dysfunction and bone loss in staphylococcal bone and joint infections.
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