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Circulating microRNA let?7e is decreased in knee osteoarthritis, accompanied by elevated apoptosis and reduced autophagy.

ABSTRACT: Knee osteoarthritis (KOA) is a major cause of leg disability in the elderly population. Recently, the expression levels of circulating microRNA (miRNA) let?7e have been reported to be significantly reduced in KOA. The aims of the present study were to assess the feasibility of let?7e as a serum marker for detecting KOA and to explore the underlying mechanisms of its involvement. Based on previous studies and bioinformatics analysis, let?7e may regulate apoptosis and autophagy of articular chondrocytes. A total of 10 patients with KOA and 10 patients with trauma without KOA were recruited to examine the levels of let?7e in peripheral blood. Subsequently, KOA rat models were established, and the levels of let?7e in the cartilage and serum were examined, the expression of apoptotic proteins and autophagy?related proteins in the cartilage were investigated, and apoptotic and autophagic activities of primary cultured chondrocytes were also detected. In patients with KOA, let?7e levels in the peripheral serum were significantly decreased compared with the control group, and this result was confirmed in the peripheral serum and cartilage of KOA rats. In addition, the expression levels of proteins involved in the apoptotic pathway were increased in the cartilage of KOA rats, and apoptotic activity was increased. The expression of autophagy?related proteins beclin 1 and microtubule associated protein 1 light chain 3 ? (LC3B) II/LC3BI in the articular cartilage of KOA rats was lower compared with the controls, and autophagy was decreased. Si?Miao?San (SMS) treatment restored the expression of let?7e and reversed the changes in apoptosis and autophagy. Therefore, the present study provided additional evidence that circulating let?7e may be a potential serum biomarker for the diagnosis and treatment of KOA. Elevated apoptosis levels and decreased autophagy levels of cartilage tissue are involved in KOA, and treatment with SMS may reverse these effects.

SUBMITTER: Feng L

PROVIDER: S-EPMC7138275 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Circulating microRNA let‑7e is decreased in knee osteoarthritis, accompanied by elevated apoptosis and reduced autophagy.

Feng Lei L Feng Chun C Wang Chang-Xing CX Xu Dan-Yi DY Chen Jun-Jie JJ Huang Jie-Feng JF Tan Pan-Li PL Shen Jin-Ming JM

International journal of molecular medicine 20200310 5

Knee osteoarthritis (KOA) is a major cause of leg disability in the elderly population. Recently, the expression levels of circulating microRNA (miRNA) let‑7e have been reported to be significantly reduced in KOA. The aims of the present study were to assess the feasibility of let‑7e as a serum marker for detecting KOA and to explore the underlying mechanisms of its involvement. Based on previous studies and bioinformatics analysis, let‑7e may regulate apoptosis and autophagy of articular chondr ...[more]

PMID: 32323821

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Project description:Anterior cruciate ligament (ACL) injury predisposes individuals to early-onset knee joint osteoarthritis (OA). Abnormal joint loading is apparent after ACL injury and reconstruction. The relationship between altered joint biomechanics and the development of knee OA is unknown.Altered knee joint kinetics and medial compartment contact forces initially after injury and reconstruction are associated with radiographic knee OA 5 years after reconstruction.Case-control study; Level of evidence, 3.Individuals with acute, unilateral ACL injury completed gait analysis before (baseline) and after (posttraining) preoperative rehabilitation and at 6 months, 1 year, and 2 years after reconstruction. Surface electromyographic and knee biomechanical data served as inputs to an electromyographically driven musculoskeletal model to estimate knee joint contact forces. Patients completed radiographic testing 5 years after reconstruction. Differences in knee joint kinetics and contact forces were compared between patients with and those without radiographic knee OA.Patients with OA walked with greater frontal plane interlimb differences than those without OA (nonOA) at baseline (peak knee adduction moment difference: 0.00 ± 0.08 N·m/kg·m [nonOA] vs -0.15 ± 0.09 N·m/kg·m [OA], P = .014; peak knee adduction moment impulse difference: -0.001 ± 0.032 N·m·s/kg·m [nonOA] vs -0.048 ± 0.031 N·m·s/kg·m [OA], P = .042). The involved limb knee adduction moment impulse of the group with osteoarthritis was also lower than that of the group without osteoarthritis at baseline (0.087 ± 0.023 N·m·s/kg·m [nonOA] vs 0.049 ± 0.018 N·m·s/kg·m [OA], P = .023). Significant group differences were absent at posttraining but reemerged 6 months after reconstruction (peak knee adduction moment difference: 0.02 ± 0.04 N·m/kg·m [nonOA] vs -0.06 ± 0.11 N·m/kg·m [OA], P = .043). In addition, the OA group walked with lower peak medial compartment contact forces of the involved limb than did the group without OA at 6 months (2.89 ± 0.52 body weight [nonOA] vs 2.10 ± 0.69 body weight [OA], P = .036).Patients who had radiographic knee OA 5 years after ACL reconstruction walked with lower knee adduction moments and medial compartment joint contact forces than did those patients without OA early after injury and reconstruction.

Project description:BackgroundOsteoarthritis (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.MethodsForty-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.ResultsThe percentages of total, CD8αα, and CD8αβ MAIT cells were higher in patients with OA compared to healthy controls. The percentages of total and CD8αα MAIT cells were higher in patients with multi-joint OA (MOA) compared to patients with knee-only OA (KOA). Plasma IFN-γ and TNF-α levels were elevated in patients with OA compared to healthy controls, and there was a positive correlation between plasma IFN-γ levels and the percentages of total, CD8αα, and CD8αβ MAIT cells. Plasma IFN-γ 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 CD8αα 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.ConclusionsMAIT 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.

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Dataset Information

Circulating microRNA let?7e is decreased in knee osteoarthritis, accompanied by elevated apoptosis and reduced autophagy.

Publications

Circulating microRNA let‑7e is decreased in knee osteoarthritis, accompanied by elevated apoptosis and reduced autophagy.

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