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Neutrophil-derived MRP-14 is up-regulated in infectious osteomyelitis and stimulates osteoclast generation
Ulrike Dapunt1, Thomas Giese2, Susanne Maurer2
1*Department of Orthopaedics and Institutes of Immunology and Pathology, University of Heidelberg, Germany ulrike.dapunt@med.uni-heidelberg.de.
Abstract:
Bone infections of patients with joint replacement by endoprosthesis (so called "periprosthetic joint infection") pose a severe problem in the field of orthopedic surgery. The diagnosis is often difficult, and treatment is, in most cases, complicated and prolonged. Patients often require an implant exchange surgery, as the persistent infection and the accompanying inflammation lead to tissue damage with bone degradation and consequently, to a loosening of the implant. To gain insight into the local inflammatory process, expression of the proinflammatory cytokine MRP-14, a major content of neutrophils, and its link to subsequent bone degradation was evaluated. We found MRP-14 prominently expressed in the affected tissue of patients with implant-associated infection, in close association with the chemokine CXCL8 and a dense infiltrate of neutrophils and macrophages. In addition, the number of MRP-14-positive cells correlated with the presence of bone-resorbing osteoclasts. MRP-14 plasma concentrations were significantly higher in patients with implant-associated infection compared with patients with sterile inflammation or healthy individuals, advocating MRP-14 as a novel diagnostic marker. A further biologic activity of MRP-14 was detected: rMRP-14 directly induced the differentiation of monocytes to osteoclasts, thus linking the inflammatory response in implant infections with osteoclast generation, bone degradation, and implant loosening.
Insights
Periprosthetic joint infections cause bone loss and implant loosening. The proinflammatory cytokine MRP-14 is linked to bone degradation and may serve as a diagnostic marker for these challenging orthopedic infections.
Area of Science:
- Orthopedic Surgery
- Immunology
- Biochemistry
Background:
- Periprosthetic joint infections (PJIs) are a severe complication of orthopedic implants, leading to significant morbidity.
- Diagnosis and treatment of PJIs are challenging, often necessitating implant revision due to infection-induced bone degradation and loosening.
Purpose of the Study:
- To investigate the role of the proinflammatory cytokine MRP-14 in the inflammatory process of PJIs.
- To evaluate the association between MRP-14 expression, immune cell infiltration, and bone degradation in PJIs.
- To determine the diagnostic potential of MRP-14 in implant-associated infections.
Main Methods:
- Analysis of MRP-14 expression in tissue samples from patients with PJIs.
- Correlation of MRP-14-positive cells with immune cell infiltrates (neutrophils, macrophages) and osteoclasts.
- Measurement of plasma MRP-14 concentrations in patients with PJIs, sterile inflammation, and healthy controls.
- In vitro assessment of recombinant MRP-14's effect on monocyte differentiation into osteoclasts.
Main Results:
- MRP-14 was highly expressed in infected tissues, co-localizing with CXCL8, neutrophils, macrophages, and osteoclasts.
- The number of MRP-14-positive cells correlated with osteoclast presence, indicating a link to bone resorption.
- Elevated MRP-14 plasma levels were observed in patients with PJIs compared to controls.
- Recombinant MRP-14 directly promoted monocyte differentiation into osteoclasts.
Conclusions:
- MRP-14 plays a significant role in the inflammatory response during PJIs, driving osteoclastogenesis and subsequent bone degradation.
- MRP-14 is a potential novel diagnostic biomarker for implant-associated infections.
- Understanding MRP-14's function offers insights into mechanisms of implant loosening and potential therapeutic targets.
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