Dataset Information

Elevated frequencies of total and MAIT cell subsets in patients with knee osteoarthritis.

ABSTRACT: Background:Osteoarthritis (OA) is characterized by the degeneration of joint cartilage, with concomitant changes in the synovium and subchondral bone. Recently, the inflammatory response and involvement of several types of T-cells has been implicated in the development of OA. This study investigated the frequency of MR1-restricted mucosal-associated invariant T (MAIT) cells in patients with knee OA. Methods:Forty-five patients recently diagnosed with knee OA and 21 age- and gender-matched healthy controls were recruited for this study. Percentages of circulating MAIT cells were assessed by flow cytometry. Plasma cytokine levels were measured using cytometric bead arrays. Associations between the percentages of MAIT cells, plasma cytokine levels, and clinical parameters of OA (erythrocyte sedimentation rate [ESR] and the Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) were analyzed using the Spearman correlation test. Results:The percentages of total, CD8??, and CD8?? MAIT cells were higher in patients with OA compared to healthy controls. The percentages of total and CD8?? MAIT cells were higher in patients with multi-joint OA (MOA) compared to patients with knee-only OA (KOA). Plasma IFN-? and TNF-? levels were elevated in patients with OA compared to healthy controls, and there was a positive correlation between plasma IFN-? levels and the percentages of total, CD8??, and CD8?? MAIT cells. Plasma IFN-? and IL-17 levels were higher in patients with MOA compared to healthy controls or patients with KOA. There were positive correlations between the percentages of total and CD8?? MAIT cells and clinical parameters (ESR and WOMAC scores) in patients with OA or MOA. Binary logistic regression analysis shown the frequency of MAIT cells was associated with the risk of OA. Conclusions:MAIT cells and their subpopulations were significantly increased in patients with OA and have potential as biological markers of OA disease severity, especially in patients with MOA.

SUBMITTER: Zhao D

PROVIDER: S-EPMC6686836 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Elevated frequencies of total and MAIT cell subsets in patients with knee osteoarthritis.

Zhao Ding D Zhong Wei W Han Dongfeng D Li Yingbo Y Jiang Yanfang Y Gu Guishan G

PeerJ 20190805

<h4>Background</h4>Osteoarthritis (OA) is characterized by the degeneration of joint cartilage, with concomitant changes in the synovium and subchondral bone. Recently, the inflammatory response and involvement of several types of T-cells has been implicated in the development of OA. This study investigated the frequency of MR1-restricted mucosal-associated invariant T (MAIT) cells in patients with knee OA.<h4>Methods</h4>Forty-five patients recently diagnosed with knee OA and 21 age- and gender ...[more]

PMID: 31404411

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Project description:Arthrofibrosis is characterized by excessive extracellular matrix (ECM) deposition that results in restricted joint motion after total knee arthroplasty (TKA). Current surgical and pharmacologic treatment options are limited. Therefore, an in vitro model for joint myofibroblastogenesis is valuable to investigate the arthrofibrotic process and identify diagnostic biomarkers and treatment options. In this study, we obtained intraoperative posterior capsule (PC), quadriceps tendon (QT), and suprapatellar pouch (SP) tissue from knees of four patients undergoing primary TKA for osteoarthritis and characterized primary outgrowth cells from these tissues in the absence and presence of transforming growth factor beta 1 (TGFβ1), a pro-myofibroblastic cytokine. Light microscopy of knee outgrowth cells revealed spindle-shaped cells while immunofluorescence (IF) established staining for the fibroblast-specific antigen TE-7 and Vimentin, which are characteristics of fibroblasts. These fibroblasts differentiate readily into myofibroblasts as highlighted by enhanced alpha smooth muscle actin (ACTA2) mRNA and protein expression and increased collagen mRNA (i.e., collagen type 1 (COL1A1) and collagen type 3 (COL3A1)) expression and collagenous matrix deposition in the presence of TGFβ1. Of note, these studies also revealed that knee-derived fibroblasts are more sensitive to TGFβ1-mediated myofibroblastogenesis than adipose-derived mesenchymal stem cells. Importantly, while outgrowth fibroblasts isolated from four patients and three anatomical regions exhibit similar gene expression profiles, these knee fibroblasts form a unique gene expression cluster within the fibroblast niche as revealed by RNA-sequencing analysis. In conclusion, our study provides a fibroblast/myofibroblast model of outgrowth knee cells derived from patients undergoing primary TKA that can be employed to assess myofibroblast-related processes and test novel pharmacological strategies in vitro for arthrofibrosis.

Project description:Reduced external knee adduction moments in the second half of stance after total hip replacement have been reported in hip osteoarthritis patients. This reduction is thought to shift the load from the medial to the lateral knee compartment and as such increase the risk for knee osteoarthritis. The knee adduction moment is a surrogate for the load distribution between the medial and lateral compartments of the knee and not a valid measure for the tibiofemoral contact forces which are the result of externally applied forces and muscle forces. The purpose of this study was to investigate whether the distribution of the tibiofemoral contact forces over the knee compartments in unilateral hip osteoarthritis patients 1 year after receiving a primary total hip replacement differs from healthy controls. Musculoskeletal modeling on gait was performed in OpenSim using the detailed knee model of Lerner et al. (2015) for 19 patients as well as for 15 healthy controls of similar age. Knee adduction moments were calculated by the inverse dynamics analysis, medial and lateral tibiofemoral contact forces with the joint reaction force analysis. Moments and contact forces of patients and controls were compared using Statistical Parametric Mapping two-sample t-tests. Knee adduction moments and medial tibiofemoral contact forces of both the ipsi- and contralateral leg were not significantly different compared to healthy controls. The contralateral leg showed 14% higher medial tibiofemoral contact forces compared to the ipsilateral (operated) leg during the second half of stance. During the first half of stance, the lateral tibiofemoral contact force of the contralateral leg was 39% lower and the ratio 32% lower compared to healthy controls. In contrast, during the second half of stance the forces were significantly higher (39 and 26%, respectively) compared to healthy controls. The higher ratio indicates a changed distribution whereas the increased lateral tibiofemoral contact forces indicate a higher lateral knee joint loading in the contralateral leg in OA patients after total hip replacement (THR). Musculoskeletal modeling using a detailed knee model can be useful to detect differences in the load distribution between the medial and lateral knee compartment which cannot be verified with the knee adduction moment.

Dataset Information

Elevated frequencies of total and MAIT cell subsets in patients with knee osteoarthritis.

Publications

Elevated frequencies of total and MAIT cell subsets in patients with knee osteoarthritis.

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