Dataset Information

Tensile strain and altered synovial tissue metabolism in human knee osteoarthritis.

ABSTRACT: Synovium is critical for maintaining joint homeostasis and may contribute to mechanobiological responses during joint movement. We investigated mechanobiological responses of whole synovium from patients with late-stage knee osteoarthritis (OA). Synovium samples were collected during total knee arthroplasty and assigned to histopathology or cyclic 10% tensile strain loading, including (1) static (control); (2) low-frequency (0.3 Hz); and iii) high-frequency (1.0 Hz) for 30-min. After 6-h incubation, tissues were bisected for RNA isolation and immunostaining (3-nitrotyrosine; 3-NT). RNA sequencing was analyzed for differentially expressed genes and pathway enrichment. Cytokines and lactate were measured in conditioned media. Compared to controls, low-frequency strain induced enrichment of pathways related to interferon response, Fc-receptor signaling, and cell metabolism. High-frequency strain induced enrichment of pathways related to NOD-like receptor signaling, high metabolic demand, and redox signaling/stress. Metabolic and redox cell stress was confirmed by increased release of lactate into conditioned media and increased 3-NT formation in the synovial lining. Late-stage OA synovial tissue responses to tensile strain include frequency-dependent increases in inflammatory signaling, metabolism, and redox biology. Based on these findings, we speculate that some synovial mechanobiological responses to strain may be beneficial, but OA likely disturbs synovial homeostasis leading to aberrant responses to mechanical stimuli, which requires further validation.

SUBMITTER: Philpott HT

PROVIDER: S-EPMC9576717 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Tensile strain and altered synovial tissue metabolism in human knee osteoarthritis.

Philpott Holly T HT Birmingham Trevor B TB Fiset Benoit B Walsh Logan A LA Coleman Mitchell C MC Séguin Cheryle A CA Appleton C Thomas CT

Scientific reports 20221017 1

Synovium is critical for maintaining joint homeostasis and may contribute to mechanobiological responses during joint movement. We investigated mechanobiological responses of whole synovium from patients with late-stage knee osteoarthritis (OA). Synovium samples were collected during total knee arthroplasty and assigned to histopathology or cyclic 10% tensile strain loading, including (1) static (control); (2) low-frequency (0.3 Hz); and iii) high-frequency (1.0 Hz) for 30-min. After 6-h incubat ...[more]

PMID: 36253398

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Project description:BackgroundSynovitis occurring frequently in osteoarthritis (OA) may be a targeted outcome. There are no data examining whether synovitis changes following intra-articular intervention.MethodsPersons aged 40 years and older with painful knee OA participated in an open label trial of intra-articular steroid therapy. At all time points they completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. They had a contrast-enhanced (CE) MRI immediately prior to an intra-articular steroid injection with a repeat scan within 20 days. Response status was assessed using the Osteoarthritis Research Society International (OARSI) response criteria. OARSI responders were followed until their pain relapsed either within 20% of baseline or 6 months, shortly after which a third MRI was performed. Synovial tissue volume (STV) was measured on postcontrast knee images. We looked at changes in the STV and in pain, and their association.Results120 subjects with preinjection and postinjection CE MRI were followed. Their mean age was 62.3 years (SD=10.3) and 62 (52%) were women. The median time between injection and follow-up scan was 8 days (IQR 7-14 days). 85/120 (71%) were OARSI responders. Pain decreased (mean change in KOOS=+23.9; 95% CI 20.1 to 27.8, p<0.001) following steroid injection, as did mean STV (mean change=-1071 mm(3); 95% CI -1839 mm(3) to -303 mm(3), p=0.01). Of the 80 who returned for a third MRI, pain relapsed in 57, and in the 48 of those with MRI data, STV increased between follow-up and final visit (+1220 mm(3); 95% CI 25 mm(3) to 2414 mm(3), p=0.05). 23 were persistent responders at 6 months and, in these, STV did not increase (mean change=-202 mm(3); 95% CI -2008 mm(3) to 1604 mm(3), p=0.83). Controlling for variation over time, there was a significant association between synovitis volume and KOOS pain (b coefficient-change in KOOS pain score per 1000 mm(3) change in STV=-1.13; 95% CI -1.87 to -0.39, p=0.003), although STV accounted for only a small proportion of the variance in change in pain.ConclusionsSynovial tissue volume in knee OA shrinks following steroid therapy, and rebounds in those whose pain relapses. It can be considered a treatment target in symptomatic knee OA.Trial registration numberISRCTN07329370.

Project description:ObjectiveSynovial membrane inflammation is common in osteoarthritis (OA) and increases cartilage injury. However, synovial fluid and histology studies suggest that OA inflammatory responses are not homogeneous. Greater understanding of these responses may provide new insights into OA disease mechanisms. We undertook this study to develop a novel multiparameter approach to phenotype synovial responses in knee OA.MethodsCell composition and soluble protein production were measured by flow cytometry and multiplex enzyme-linked immunosorbent assay in synovium collected from OA patients undergoing knee replacement surgery (n = 35).ResultsTesting disaggregation conditions showed that aggressive digestion improved synovial cell yield and mesenchymal staining by flow cytometry, but it negatively impacted CD4+ T cell and CD56+ natural killer cell staining. Less aggressive digestion preserved these markers and showed highly variable T cell infiltration (range 0-43%; n = 32). Correlation analysis identified mesenchymal subpopulations associated with different nonmesenchymal populations, including macrophages and T cells (CD45+CD11b+HLA-DR+ myeloid cells with PDPN+CD73+CD90-CD34- mesenchymal cells [r = 0.65, P < 0.0001]; and CD45+CD3+ T cells with PDPN+CD73+CD90+CD34+ mesenchymal cells [r = 0.50, P = 0.003]). Interleukin-6 (IL-6) measured by flow cytometry strongly correlated with IL-6 released by ex vivo culture of synovial tissue (r = 0.59, P = 0.0012) and was highest in mesenchymal cells coexpressing CD90 and CD34. IL-6, IL-8, complement factor D, and IL-10 release correlated positively with tissue cellularity (P = 0.0042, P = 0.018, P = 0.0012, and P = 0.038, respectively). Additionally, increased CD8+ T cell numbers correlated with retinol binding protein 4 (P = 0.033). Finally, combining flow cytometry and multiplex data identified patient clusters with different types of inflammatory responses.ConclusionWe used a novel approach to analyze OA synovium, identifying patient-specific inflammatory clusters. Our findings indicate that phenotyping synovial inflammation may provide new insights into OA patient heterogeneity and biomarker development.

Dataset Information

Tensile strain and altered synovial tissue metabolism in human knee osteoarthritis.

Publications

Tensile strain and altered synovial tissue metabolism in human knee osteoarthritis.

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