Both systemic and local lipopolysaccharide (LPS) burden are associated with knee OA severity and inflammation
Z Y Huang1, T Stabler2, F X Pei3
1Department of Orthopedic Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, People's Republic of China; Duke Molecular Physiology Institute, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
Objective:
The microbiome is recognized as a new frontier in medicine with connections to a variety of diseases. We aimed to evaluate the association of lipopolysaccharide (LPS), a key pro-inflammatory product of the microbiome, with severity of inflammation, symptoms and radiographic abnormalities of knee osteoarthritis (OA).
Design:
LPS was measured using a recombinant Factor C (rFC) assay, carefully optimized for systemic and synovial fluid (SF) analyses. LPS binding protein (LBP) was tested in both serum and SF of 25 patients (31 knees) from the Etarfolatide cohort for association with OA phenotypic outcomes. Models were adjusted for age, gender and body mass index.
Results:
Based on LPS spike-and-recovery, both serum and SF dilutions of 0.1% were required to achieve recovery rates of at least 75% in all test specimens. Low coefficients of variation (CVs) (<10%) were achieved with both serum and SF dilutions <0.2%. Serum LPS and LBP were associated with the abundance of activated macrophages in the knee joint capsule and synovium. SF LPS and LBP were associated with the abundance of activated macrophages in the synovium. Serum LPS, LBP and SF LPS were associated with knee osteophyte severity. SF LPS was positively associated with knee joint space narrowing (JSN) severity and total WOMAC score. SF LBP was positively associated with self-reported knee pain score.
Conclusion:
These data strongly support a role for LPS in the pathogenesis and severity of structural abnormalities and symptoms of knee OA.
Insights
Lipopolysaccharide (LPS), a microbiome product, is linked to knee osteoarthritis (OA) severity. Higher LPS levels in synovial fluid correlate with joint space narrowing and pain, supporting its role in OA.
Area of Science:
- Microbiome research
- Immunology
- Rheumatology
Background:
- The microbiome is a significant factor in various diseases.
- Lipopolysaccharide (LPS) is a pro-inflammatory molecule produced by the microbiome.
Purpose of the Study:
- To investigate the association between LPS and knee osteoarthritis (OA).
- To evaluate LPS's link to inflammation severity, OA symptoms, and radiographic changes.
Main Methods:
- LPS and LPS binding protein (LBP) were measured in serum and synovial fluid (SF) using a recombinant Factor C (rFC) assay.
- Associations with OA phenotypes were analyzed in 25 patients, adjusting for age, gender, and BMI.
Main Results:
- Serum and SF LPS/LBP correlated with activated macrophages in knee tissues.
- Serum LPS/LBP and SF LPS were linked to osteophyte severity.
- SF LPS showed positive associations with joint space narrowing and WOMAC scores.
- SF LBP correlated with self-reported knee pain.
Conclusions:
- LPS plays a role in the development and severity of knee OA.
- Microbiome-derived LPS contributes to OA pathogenesis, inflammation, and symptoms.
