Mode of injury and level of synovitis alter inflammatory chondrocyte gene expression and associated pathways.

Autor: Libke ML; Department of Orthopaedic Surgery, Duke University, Durham, NC, USA.; Department of Biomedical Engineering, Duke University, Durham, NC, USA.; School of Medicine, Indiana University, Indianapolis, USA., Cunningham DJ; Department of Orthopaedic Surgery, Duke University, Durham, NC, USA.; School of Medicine, Duke University, Durham, NC, USA., Furman BD; Department of Orthopaedic Surgery, Duke University, Durham, NC, USA.; School of Medicine, Duke University, Durham, NC, USA., Yi JS; Department of Surgery, Duke University, Durham, NC, USA., Brunger JM; Department of Orthopaedic Surgery, Duke University, Durham, NC, USA.; Department of Biomedical Engineering, Duke University, Durham, NC, USA.; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA., Kraus VB; Department of Orthopaedic Surgery, Duke University, Durham, NC, USA.; School of Medicine, Duke University, Durham, NC, USA.; Department of Medicine, Duke Molecular Physiology Institute, Durham, NC, USA., Guilak F; Washington University in St. Louis, St. Louis, MO, USA.; Shriners Hospitals for Children, St. Louis, MO, USA., McNulty AL; Department of Orthopaedic Surgery, Duke University, Durham, NC, USA.; Department of Biomedical Engineering, Duke University, Durham, NC, USA.; Department of Pathology, Duke University, Durham, NC, USA., Olson SA; Department of Orthopaedic Surgery, Duke University, Durham, NC, USA. steven.olson@duke.edu.; School of Medicine, Duke University, Durham, NC, USA. steven.olson@duke.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Nov 21; Vol. 14 (1), pp. 28917. Date of Electronic Publication: 2024 Nov 21.
DOI: 10.1038/s41598-024-71964-5
Abstrakt: Although various joint injuries result in post-traumatic osteoarthritis (PTOA), differences in chondrocyte response to specific injuries, such as blunt compression or fracture, are unclear. Furthermore, the role of underlying joint inflammation, or synovitis, is often not considered. We investigated how injury mechanisms and underlying synovitis affect chondrocyte gene expression using osteochondral injury models with synovial co-culture. We hypothesized that the state of synovitis as well as the mechanism of biomechanical cartilage injury differentially alter the gene expression of chondrocytes and that these responses are regulated by the pro-inflammatory cytokine interleukin 1 (IL-1). The mechanism of injury and level of synovial inflammation both significantly regulated chondrocyte gene expression and associated pathways, uncovering distinct characteristics of fracture and compression injury mechanisms. Targeting IL-1 following injury reduced the inflammatory response and could have clinical implications. The results from this study show that crosstalk between biomechanics and inflammation in the context of synovitis and cartilage injury mechanism is an important consideration for PTOA.
Competing Interests: Competing interests: Dr. Guilak is an employee and shareholder of Cytex Therapeutics, Inc. All other co-authors have no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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