The alarmins high mobility group box protein 1 and S100A8/A9 display different inflammatory profiles after acute knee injury

C Aulin; S Larsson; T Vogl; J Roth; A Åkesson; P Swärd; R Heinbäck; H Erlandsson Harris; A Struglics

doi:10.1016/j.joca.2022.06.009

The alarmins high mobility group box protein 1 and S100A8/A9 display different inflammatory profiles after acute knee injury

Osteoarthritis Cartilage. 2022 Sep;30(9):1198-1209. doi: 10.1016/j.joca.2022.06.009. Epub 2022 Jul 6.

Authors

C Aulin¹, S Larsson², T Vogl³, J Roth³, A Åkesson⁴, P Swärd², R Heinbäck⁵, H Erlandsson Harris⁶, A Struglics²

Affiliations

¹ Center for Molecular Medicine, Department of Medicine Solna, Karolinska Institutet, and Division of Rheumatology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. Electronic address: cecilia.aulin@ki.se.
² Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lund, Sweden.
³ University of Muenster, Institute of Immunology, Münster, Germany.
⁴ Clinical Studies Sweden, Forum South, Skåne University Hospital, Lund, Sweden.
⁵ Center for Molecular Medicine, Department of Medicine Solna, Karolinska Institutet, and Division of Rheumatology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
⁶ Center for Molecular Medicine, Department of Medicine Solna, Karolinska Institutet, and Division of Rheumatology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden; Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.

PMID: 35809846
DOI: 10.1016/j.joca.2022.06.009

Abstract

Objective: To compare the concentrations of high mobility group box 1 protein (HMGB1) and S100A8/A9 in synovial fluid between patients with knee injuries and osteoarthritis (OA), and knee healthy subjects. To investigate associations of alarmin levels with different joint injuries and with biomarkers of inflammation, Wnt signaling, complement system, bone and cartilage degradation.

Methods: HMGB1 and S100A8/A9 were measured in synovial fluid by immunoassays in patients with knee injuries, with OA and from knee healthy subjects, and were related to time from injury and with biomarkers obtained from previous studies. Hierarchical cluster and enrichment analyses of biomarkers associated to HMGB1 and S100A8/A9 were performed.

Results: The synovial fluid HMGB1 and S100A8/A9 concentrations were increased early after knee injury; S100A8/A9 levels were negatively associated to time after injury and was lower in the old compared to recent injury group, while HMGB1 was not associated to time after injury. The S100A8/A9 levels were also increased in OA. The initial inflammatory response was similar between the alarmins, and HMGB1 and S100A8/A9 shared 9 out of 20 enriched pathways. The alarmins displayed distinct response profiles, HMGB1 being associated to cartilage biomarkers while S100A8/A9 was associated to proinflammatory cytokines.

Conclusions: HMGB1 and S100A8/A9 are increased as an immediate response to knee trauma. While they share many features in inflammatory and immunoregulatory mechanisms, S100A8/A9 and HMGB1 are associated to different downstream responses, which may have impact on the OA progression after acute knee injuries.

Keywords: Alarmins; HMGB1; Knee injury; Osteoarthritis; S100A8/A9.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alarmins
Biomarkers
Calgranulin A / metabolism*
Calgranulin B / metabolism*
HMGB1 Protein / metabolism*
Humans
Knee Injuries* / metabolism
Knee Injuries* / pathology
Osteoarthritis / metabolism

Substances

Alarmins
Biomarkers
Calgranulin A
Calgranulin B
HMGB1 Protein
HMGB1 protein, human
S100A8 protein, human
S100A9 protein, human