Osteoarthritis

Glyn-Jones, S; Palmer, Antony; Agricola, Rintje; Price, Andrew; Vincent, Tonia L.; Weinans, Harrie; Carr, Andrew

doi:10.1016/s0140-6736(14)60802-3

Cited by 2,112 publications

(1,451 citation statements)

References 132 publications

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“…Osteoarthritis (OA) is a highly prevalent and degenerative joint disorder, causing pain and functional disability, and representing an enormous clinical and financial burden 1. OA is traditionally characterised by erosion of cartilage and subchondral bone sclerosis.…”

Section: Introductionmentioning

confidence: 99%

Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2

et al. 2018

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ObjectivesTo investigate the roles and regulatory mechanisms of synovial macrophages and their polarisation in the development of osteoarthritis (OA).MethodsSynovial tissues from normal patients and patients with OA were collected. M1 or M2-polarised macrophages in synovial tissues of patients with OA and OA mice were analysed by immunofluorescence and immunohistochemical staining. Mice with tuberous sclerosis complex 1 (TSC1) or Rheb deletion specifically in the myeloid lineage were generated and subjected to intra-articular injection of collagenase (collagenase-induced osteoarthritis, CIOA) and destabilisation of the medial meniscus (DMM) surgery to induce OA. Cartilage damage and osteophyte size were measured by Osteoarthritis Research Society International score and micro-CT, respectively. mRNA sequencing was performed in M1 and control macrophages. Mice and ATDC5 cells were treated with R-spondin-2 (Rspo2) or anti-Rspo2 to investigate the role of Rspo2 in OA.ResultsM1 but not M2-polarised macrophages accumulated in human and mouse OA synovial tissue. TSC1 deletion in the myeloid lineage constitutively activated mechanistic target of rapamycin complex 1 (mTORC1), increased M1 polarisation in synovial macrophages and exacerbated experimental OA in both CIOA and DMM models, while Rheb deletion inhibited mTORC1, enhanced M2 polarisation and alleviated CIOA in mice. The results show that promoting the macrophage M1 polarisation leads to exacerbation of experimental OA partially through secretion of Rspo2 and activation of β-catenin signalling in chondrocytes.ConclusionsSynovial macrophage M1 polarisation exacerbates experimental CIOA partially through Rspo2. M1 macrophages and Rspo2 are potential therapeutic targets for OA treatment.

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Section: Introductionmentioning

confidence: 99%

Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2

et al. 2018

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“…Osteoarthritis (OA) is the most common arthritis characterized by a hallmark symptom of pain, even leads to disability (1). It is well-known that OA is caused by the combined effects of genetic, biological, and biomechanical factors (2).…”

Section: Introductionmentioning

confidence: 99%

miR-4262 regulates chondrocyte viability, apoptosis, autophagy by targeting SIRT1 and activating PI3K/AKT/mTOR signaling pathway in rats with osteoarthritis

Sun

Li²,

Wei³

2017

Exp Ther Med

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Abstract. The present study aimed to investigate the effect and underlying mechanism of microRNA (miR)-4262 in the development of osteoarthritis (OA) in rats. Primary chondrocytes were separated from Sprague-Dawley rats and then treated with tumor necrosis factor-α (TNF-α). The level of miR-4262 was detected in TNF-α-treated chondrocytes, and then the miR-4262 or its target gene sirtuin type 1 (SIRT1) level was overexpressed, or knocked down. Furthermore, cell viability, cell apoptosis, cell autophagy and matrix synthesis, as well as the expressions of proteins associated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway were detected. miR-4262 was significantly overexpressed in TNF-α-treated chondrocytes compared with untreated cells (P<0.05). TNF-α treatment or miR-4262 overexpression significantly decreased cell viability, autophagy-related proteins levels and matrix synthesis-related proteins levels, as well as increased the apoptotic rate in chondrocytes (P<0.05). Overexpression of SIRT1 significantly increased cell viability, autophagy-related proteins levels and matrix synthesis-related proteins levels, as well as decreased the apoptotic rate in TNF-α-treated chondrocytes (P<0.05). In addition, the effects of miR-4262 on cell viability, cell apoptosis, cell autophagy and matrix synthesis were inhibited by SIRT1 (P<0.05). Furthermore, upregulated miR-4262 remarkably increased the expressions of phosphorylated (p)-PI3K, p-AKT and p-mTOR (P<0.05) in TNF-α treated chondrocytes. The present study revealed that the upregulation of miR-4262 may promote the occurrence and development of OA in rats by regulating cell viability, cell apoptosis, cell autophagy, and matrix synthesis. Furthermore, these roles of miR-4262 may be associated with PI3K/AKT/mTOR signaling pathway.

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“…Femoroacetabular impingement (FAI) is a common cause of hip pain and refers to the abnormal conflicting movement of the femoral head-neck (FHN) junction against the acetabular rim [1], eventually resulting in hip damage and osteoarthritis (OA) [2][3][4]. The cam type generally involves an FHN deformity and the pincer-type acetabular overcoverage [1].…”

Section: Introductionmentioning

confidence: 99%

Cam deformity and the omega angle, a novel quantitative measurement of femoral head-neck morphology: a 3D CT gender analysis in asymptomatic subjects

et al. 2016

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Objective Our objectives were to use 3D computed tomography (CT) to define head-neck morphologic gender-specific and normative parameters in asymptomatic individuals and use the omega angle (Ω°) to provide quantification data on the location and radial extension of a cam deformity. Methods We prospectively included 350 individuals and evaluated 188 asymptomatic hips that underwent semiautomated CT analysis. Different thresholds of alpha angle (α°) were considered in order to analyze cam morphology and determine Ω°. We calculated overall and gender-specific parameters for imaging signs of cam morphology (Ω°and circumferential α°). Results The 95 % reference interval limits were beyond abnormal thresholds found in the literature for cam morphology. Specifically, α°at 3/1 o´clock were 46.9°/60.8°overall, 51.8°/ 65.4°for men and 45.7°/55.3°for women. Cam prevalence, magnitude, location, and epicenter were significantly gender different. Increasing α°correlated with higher Ω°, meaning that higher angles correspond to larger cam deformities.Conclusion Hip morphometry measurements in this cohort of asymptomatic individuals extended beyond current thresholds used for the clinical diagnosis of cam deformity, and α°was found to vary both by gender and measurement location. These results suggest that α°measurement is insufficient for the diagnosis of cam deformity. Enhanced morphometric evaluation, including 3D imaging and Ω°, may enable a more accurate diagnosis. Key Points • 95% reference interval limits of cam morphotype were beyond currently defined thresholds.• Current morphometric definitions for cam-type morphotype should be applied with care.• Cam prevalence, magnitude, location, and epicenter are significantly gender different.• Cam and alpha angle thresholds should be defined according to sex/location. • Quantitative 3D morphometric assessment allows thorough and reproducible FAI diagnosis and monitoring.

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Osteoarthritis

Cited by 2,112 publications

References 132 publications

Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2

Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2

miR-4262 regulates chondrocyte viability, apoptosis, autophagy by targeting SIRT1 and activating PI3K/AKT/mTOR signaling pathway in rats with osteoarthritis

Cam deformity and the omega angle, a novel quantitative measurement of femoral head-neck morphology: a 3D CT gender analysis in asymptomatic subjects

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