Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Oct 10;26(1):176.
doi: 10.1186/s13075-024-03409-3.

Changes and associations between synovial fluid and magnetic resonance imaging markers of osteoarthritis after high tibial osteotomy

Jenna M Schulz  1   2   3 , Trevor B Birmingham  4   5   6 , Holly T Philpott  5   7 , C Thomas Appleton  5   7 , Hayden F Atkinson  5   7 , J Robert Giffin  5   6   8 , Frank Beier  5   7
Affiliations

Changes and associations between synovial fluid and magnetic resonance imaging markers of osteoarthritis after high tibial osteotomy

Jenna M Schulz et al. Arthritis Res Ther. .

Abstract

Background: Mechanobiological mechanisms of osteoarthritis (OA) are unclear. Our objectives were to explore: 1) changes in knee joint physiology using a large panel of synovial fluid biomarkers from before to one year after high tibial osteotomy (HTO) surgery, and 2) the association of changes in the synovial fluid biomarkers with the changes in MRI measures of knee effusion-synovitis and articular cartilage composition.

Methods: Twenty-six patients with symptomatic knee OA and varus alignment underwent synovial fluid aspirations and 3 T MRI before and one year after medial opening wedge HTO. Cytokine and growth factor levels in synovial fluid were measured with multiplex assays. Ontology and pathway enrichment was assessed using data protein sets with gene set enrichment analysis (GSEA), and analyzed using linear mixed effects models. MRIs were analyzed for effusion-synovitis and T2 cartilage relaxation time using manual segmentations. Changes in biomarker concentrations were correlated to changes in MRI effusion-synovitis volume and articular cartilage T2 relaxation times.

Results: Decreased enrichment in Toll-like receptor and TNF-α signalling was detected one year after HTO. The leading contributors to this reduction included IL-6, TNF-α and IL-1β, whereas the highest contributors to positive enrichment were EGF, PDGF-BB and FGF-2. Effusion-synovitis volume decreased (mean [95%CI]) one year after HTO (-2811.58 [-5094.40, -528.76mm3]). Effusion-synovitis volume was moderately correlated (r [95% CI]) with decreased MMP-1 (0.44 [0.05; 0.71]), IL-7 (0.41 [0.00; 0.69]) and IL-1β (0.59 [0.25; 0.80]) and increased MIP-1β (0.47 [0.10; 0.73]). Medial tibiofemoral articular cartilage T2 relaxation time decreased (mean [95% CI]) one year after HTO (-0.33 [-2.69; 2.05]ms). Decreased T2 relaxation time was moderately correlated to decreased Flt-3L (0.61 [0.28; 0.81]), IL-10 (0.47 [0.09; 0.73]), IP-10 (0.42; 0.03-0.70) and increased MMP-9 (-0.41 [-0.7; -0.03]) and IL-18 (-0.48 [-0.73; -0.10]).

Conclusions: Decreased aberrant knee mechanical loading in patients with OA is associated with decreased biological and imaging measures of inflammation (measured in synovial fluid and on MRI) and increased anabolic processes. These exploratory findings suggest that improvement in knee loading can produce long-term (one year) improvement in joint physiology.

Keywords: Biomarkers; Effusion-synovitis; High tibial osteotomy; Inflammation; Magnetic resonance imaging; Osteoarthritis.

PubMed Disclaimer

Conflict of interest statement

CTA is a consultant for Abbvie, Amgen, Bristol Myers Squibb, Celgene, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, Pfizer, Hoffmaan LaRoche, Sandoz, Sanofi-Genzyme, and UCB.

Figures

Fig. 1
Fig. 1
Demonstration of synovial fluid segmentation (a) and T2 relaxation (b) on MRI images
Fig. 2
Fig. 2
Leading edge analysis of the biomarkers that accounted for the negative (i.e. higher at baseline; a) and positive (i.e. lower at baseline, b) enrichment
Fig. 3
Fig. 3
Correlations (Pearson r) between one-year changes pre-to-post HTO in synovial fluid biomarkers, effusion-synovitis and T2 relaxation times. MT + MF; medial tibial + medial femoral, LT + LF; lateral tibial + lateral femoral, PAT; patellar
See this image and copyright information in PMC

References

    1. Hui AY, McCarty WJ, Masuda K, et al. A systems biology approach to synovial joint lubrication in health, injury, and disease. Wiley Interdiscip Rev: Syst Biol Med. 2012;4:15–37. - PMC - PubMed
    1. Mathiessen A, Conaghan PG. Synovitis in osteoarthritis: Current understanding with therapeutic implications. Arthritis Research and Therapy; 19. Epub ahead of print 2 February 2017. 10.1186/s13075-017-1229-9. - PMC - PubMed
    1. Aigner T, Kim HA, Roach HI. Apoptosis in osteoarthritis. Rheum Dis Clin North Am. 2004;30:639–53. - PubMed
    1. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage. 2013;21:16–21. - PubMed
    1. Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol. 2010;6:625–35. - PubMed

MeSH terms

LinkOut - more resources