Combination treatment with anti-RANKL and antibiotics for preventing joint destruction in septic arthritis
Septic arthritis, the most severe joint disease, is frequently caused by Staphylococcus aureus (S. aureus). A substantial proportion of patients with septic arthritis experience poor joint outcomes, often necessitating joint replacement surgery. Here, we show that monocyte depletion confers full protection against bone erosion in a septic arthritis mouse model. In the infected synovium, Ly6Chi monocytes exhibited increased expression of osteoclastogenesis-related molecules, including CCR2, c-Fms, and RANK. S. aureus lipoproteins induced elevated levels of RANKL, MCSF, and CCL2 in joints, with synovial fibroblasts identified as the major RANKL producer. Anti-RANKL treatment prevented bone destruction in both local and hematogenous septic arthritis murine models. Importantly, combining anti-RANKL treatment with antibiotics provided robust protection against joint damage. Our results indicate that the infiltration and transformation of monocytes into bone-destructive, osteoclast-like cells are key mechanisms in septic arthritis. Combining anti-RANKL and antibiotic therapy represents a promising therapy against this devastating disease.
Authors
- Carmen Corciulo (ORCID: https://orcid.org/0000-0002-1865-3494)
- Meghshree Deshmukh (ORCID: https://orcid.org/0000-0003-0165-0278)
- Miriam Bollmann (ORCID: https://orcid.org/0000-0003-1639-8079)
- Abukar Ali (ORCID: https://orcid.org/0000-0002-1963-3356)
- Pradeep Kumar Kopparapu (ORCID: https://orcid.org/0000-0003-3941-748X)
- Cecilia Engdahl (ORCID: https://orcid.org/0000-0002-8914-0178)
- Tao Jin (ORCID: https://orcid.org/0000-0001-9039-0628)
- Anders Jarneborn (ORCID: https://orcid.org/0000-0002-6184-7825)
- Zhicheng Hu (ORCID: https://orcid.org/0000-0002-3899-0711)
- Mattias N. D. Svensson (ORCID: https://orcid.org/0000-0001-8077-9824)
- Majd Mohammad (ORCID: https://orcid.org/0000-0002-3672-2991)
- Rille Pullerits (ORCID: https://orcid.org/0000-0002-5383-9817)
Institutions
- Guiyang Medical University (CN)
- BirdLife International (KE)
- Sahlgrenska University Hospital (SE)
- Affiliated Hospital of Guizhou Medical University (CN)
- University of Gothenburg (SE)
Publication Details
- Journal
- JCI Insight
- Published
- 2025-03-11
- DOI
- https://doi.org/10.1172/jci.insight.184954
- Citations
- 2
- Primary Topic
- Orthopedic Infections and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 4.01
Funders
- Rune och Ulla Amlövs Stiftelse för Neurologisk och Reumatologisk Forskning
- Petrus och Augusta Hedlunds Stiftelse
- National Natural Science Foundation of China
- Stiftelsen Konung Gustaf V:s 80-årsfond