Exploring longitudinal associations of histologically assessed inflammation with symptoms and radiographic damage in knee osteoarthritis: combined results of three prospective cohort studies

Minten, M.J.M.; Blom, A.B.; Snijders, G.F.; Kloppenburg, Margreet; Hoogen, F.H.J. van den; Broeder, Alfons A den; Kraan, P.M. van der; Ende, C.H.M. van den

doi:10.1016/j.joca.2018.10.014

Cited by 30 publications

(39 citation statements)

References 30 publications

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“…Additionally, tissue sampling bias may have influenced study results. Prior RA and OA studies suggest that good histologic or RNA sequencing reproducibility can be achieved with 3–4 ultrasound‐guided synovial biopsy samples or with ~150 mg tissue . We found low variability with 4 ~100‐mg OA tissue samples, but we generally used higher tissue amounts to reduce bias.…”

Section: Discussionmentioning

confidence: 70%

“…Many studies have demonstrated heterogeneity in OA synovial responses , reflecting potential differences in disease pathology. To phenotype synovial response patterns in knee OA, we combined ex vivo flow cytometry and multianalyte ELISAs after limited culture of intact tissue (Figure A).…”

Section: Resultsmentioning

confidence: 99%

“…How anatomy affects synovial responses remains an open issue in the field and requires additional comparative studies to define how synovial responses vary by distinct regional location within each patient. Finally, it is known that synovial findings change in OA as disease progresses , so a similar analysis comparing early‐ and late‐disease tissue, along with analyzing radiographic damage and additional clinical variables, is needed in future investigations.…”

Section: Discussionmentioning

confidence: 99%

“…Macroscopic visualization by arthroscopy, ultrasound, or magnetic resonance imaging suggests that up to 50% of patients with early OA have at least intermittent synovitis . However, microscopic examination demonstrates that synovial abnormalities are also frequent in early OA . Synovial changes are thought to arise from cellular activation by damage signals released during joint injury, resulting in areas of synovial lining hyperplasia and sublining immune infiltration.…”

Section: Introductionmentioning

confidence: 99%

“…Synovial histology and proinflammatory mediator expression suggest considerable variability among patients in tissue injury response . Our objective was to use multiparameter analysis to explore synovial response diversity across a late‐stage knee OA cohort, with the hope that this would provide further insight into the cellular and molecular drivers of OA pathology.…”

Section: Introductionmentioning

confidence: 99%

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Multiparameter Analysis Identifies Heterogeneity in Knee Osteoarthritis Synovial Responses

Labinsky

Panipinto

et al. 2020

Arthritis & Rheumatology

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Objective Synovial 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. Methods Cell 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). Results Testing 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. Conclusion We 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.

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Section: Discussionmentioning

confidence: 70%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Multiparameter Analysis Identifies Heterogeneity in Knee Osteoarthritis Synovial Responses

Labinsky

Panipinto

et al. 2020

Arthritis & Rheumatology

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Impaired Efferocytosis by Synovial Macrophages in Patients With Knee Osteoarthritis

Sordo

Blackler

Philpott

et al. 2023

Arthritis & Rheumatology

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Objective. Osteoarthritis (OA) exposes all joint tissues to physiologic stresses, increasing the need to clear apoptotic cells from tissues, including the synovium. We undertook this study to assess the burden of apoptotic cells in synovial tissue in patients with late-stage knee OA and to investigate whether OA impairs the macrophage-mediated clearance of apoptotic cells via efferocytosis.Methods. Synovial tissue was collected from individuals with healthy knees and patients with late-stage knee OA during arthroplasty. Synovial apoptotic cell burden was assessed by immunofluorescence for cleaved caspase 3. Efferocytosis of apoptotic Jurkat cells by CD14+ synovial tissue macrophages and peripheral blood-derived macrophages was quantified using immunofluorescence microscopy. Effects of OA on macrophage-mediated efferocytosis were modeled by stimulating blood-derived macrophages with synovial fluid collected from individuals with healthy knees and patients with early-or late-stage knee OA.Results. Patients with late-stage knee OA had more apoptotic synovial cells compared to healthy individuals. There was a marked reduction in the fraction of synovial tissue macrophages engaging in efferocytosis and the quantity of material efferocytosed by individual macrophages in OA patients. Blood-derived macrophages exposed to synovial fluid from patients with knee OA recapitulated the defective efferocytosis, with the greatest effect from patients with early-stage knee OA and higher disease activity (pain and inflammation).Conclusion. Apoptotic cells accumulate in the synovium of patients with late-stage knee OA. Our results suggest that OA impairs critical homeostatic functions of synovial macrophages, leading to accumulation of apoptotic cells.

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The potential role of synovial cells in the progression and treatment of osteoarthritis

Zou

Han

Yang³

et al. 2023

Exploration

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Osteoarthritis (OA), the commonest arthritis, is characterized by the progressive destruction of cartilage, leading to disability. The Current early clinical treatment strategy for OA often centers on anti‐inflammatory or analgesia medication, weight loss, improved muscular function and articular cartilage repair. Although these treatments can relieve symptoms, OA tends to be progressive, and most patients require arthroplasty at the terminal stages of OA. Recent studies have shown a close correlation between joint pain, inflammation, cartilage destruction and synovial cells. Consequently, understanding the potential mechanisms associated with the action of synovial cells in OA could be beneficial for the clinical management of OA. Therefore, this review comprehensively describes the biological functions of synovial cells, the synovium, together with the pathological changes of synovial cells in OA, and the interaction between the cartilage and synovium, which is lacking in the present literature. Additionally, therapeutic approaches based on synovial cells for OA treatment are further discussed from a clinical perspective, highlighting a new direction in the treatment of OA.

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Exploring longitudinal associations of histologically assessed inflammation with symptoms and radiographic damage in knee osteoarthritis: combined results of three prospective cohort studies

Cited by 30 publications

References 30 publications

Multiparameter Analysis Identifies Heterogeneity in Knee Osteoarthritis Synovial Responses

Multiparameter Analysis Identifies Heterogeneity in Knee Osteoarthritis Synovial Responses

Impaired Efferocytosis by Synovial Macrophages in Patients With Knee Osteoarthritis

The potential role of synovial cells in the progression and treatment of osteoarthritis

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