Osteoarthritis year in review 2019: epidemiology and therapy

Kloppenburg, Margreet; Bérenbaum, Francis

doi:10.1016/j.joca.2020.01.002

Cited by 406 publications

(342 citation statements)

References 40 publications

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“…The molecular cascade underlying the pathogenesis of these two joint diseases are not well understood. Osteoarthritis leads to cartilage degeneration, reviewed in [158], while rheumatoid arthritis is an autoimmune and inflamatory disease associated with an increase of synovial fibroblasts leading to joint degeneration [159]. TNFα levels are increased in the synovial fluid of patients with osteoarthritis and rheumatoid arthritis [25] and reduce the expression of Col2a1, Acan (Aggrecan), and Hapln1 through EGR1 recruitment to their promoters [25].…”

Section: Egr1 and Matrix Production In Rheumatoid Arthritis And Osteomentioning

confidence: 99%

EGR1 Transcription Factor is a Multifaceted Regulator of Matrix Production in Tendons and Other Connective Tissues

Havis

Duprez

2020

IJMS

359

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Although the transcription factor EGR1 is known as NGF1-A, TIS8, Krox24, zif/268, and ZENK, it still has many fewer names than biological functions. A broad range of signals induce Egr1 gene expression via numerous regulatory elements identified in the Egr1 promoter. EGR1 is also the target of multiple post-translational modifications, which modulate EGR1 transcriptional activity. Despite the myriad regulators of Egr1 transcription and translation, and the numerous biological functions identified for EGR1, the literature reveals a recurring theme of EGR1 transcriptional activity in connective tissues, regulating genes related to the extracellular matrix. Egr1 is expressed in different connective tissues, such as tendon (a dense connective tissue), cartilage and bone (supportive connective tissues), and adipose tissue (a loose connective tissue). Egr1 is involved in the development, homeostasis, and healing processes of these tissues, mainly via the regulation of extracellular matrix. In addition, Egr1 is often involved in the abnormal production of extracellular matrix in fibrotic conditions, and Egr1 deletion is seen as a target for therapeutic strategies to fight fibrotic conditions. This generic EGR1 function in matrix regulation has little-explored implications but is potentially important for tendon repair.

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Section: Egr1 and Matrix Production In Rheumatoid Arthritis And Osteomentioning

confidence: 99%

EGR1 Transcription Factor is a Multifaceted Regulator of Matrix Production in Tendons and Other Connective Tissues

Havis

Duprez

2020

IJMS

359

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“…Osteoarthritis (OA) is the most prevalent type of musculoskeletal disorder in patients 60 years or older [1][2][3]. OA is a leading cause of pain and disability and patients with symptomatic knee OA are at an increased risk of all-cause mortality [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Proteoglycan-4 Regulates Fibroblast to Myofibroblast Transition and Expression of Fibrotic Genes in the Synovium

Qadri

Jay

Zhang

et al. 2020

Preprint

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Background: Synovial tissue fibrosis is common in advanced OA with features including the presence of stress fiber-positive myofibroblasts and deposition of cross-linked collagen type-I. Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and is a major component of synovial fluid. PRG4 is a ligand of the CD44 receptor. Our objective was to examine the role of PRG4-CD44 interaction in regulating synovial tissue fibrosis in vitro and in vivo. Methods: OA synoviocytes were treated with TGF-β ± PRG4 for 24 hours and α-SMA content was determined using immunofluorescence. Rhodamine labeled rhPRG4 was incubated with OA synoviocytes ± anti-CD44 or isotype control antibodies and cellular uptake of rhPRG4 was determined following a 30-min incubation and a-SMA expression following a 24-hour incubation. HEK-TGF-β cells were treated with TGF-β ± rhPRG4 and Smad3 phosphorylation was determined using immunofluorescence and TGF-β/Smad pathway activation was determined colorimetrically. We probed for stress fibers and focal adhesions (FAs) in TGF-β treated murine fibroblasts and fibroblast migration was quantified ± rhPRG4. Synovial expression of fibrotic markers: α-SMA, collagen type-I and PLOD2 in Prg4 gene trap (Prg4GT) and recombined Prg4GTR animals was studied at 2 and 9 months of age. Synovial expression of α-SMA and PLOD2 was determined in 2-months old Prg4GT/GT&Cd44-/- and Prg4GTR/GTR&Cd44-/- animals. Results: PRG4 reduced α-SMA content in OA synoviocytes (p<0.001). rhPRG4 was internalized by OA synoviocytes via CD44 and CD44 neutralization attenuated rhPRG4’s antifibrotic effect (p<0.05). rhPRG4 reduced pSmad3 signal in HEK-TGF-β cells (p<0.001) and TGF-β/Smad pathway activation (p<0.001). rhPRG4 reduced the number of stress fiber-positive myofibroblasts, FAs mean size, and cell migration in TGF-β treated NIH3T3 fibroblasts (p<0.05). rhPRG4 inhibited fibroblast migration in a macrophage and fibroblast co-culture model without altering active or total TGF-β levels. Synovial tissues of 9-months old Prg4GT/GT animals had higher α-SMA, collagen type-I and PLOD2 (p<0.001) content and Prg4 re-expression reduced these markers (p<0.01). Prg4 re-expression also reduced α-SMA and PLOD2 staining in CD44-deficient mice. Conclusion: PRG4 is an endogenous antifibrotic modulator in the joint and its effect on myofibroblast formation is partially mediated by CD44, but CD44 is not required to demonstrate an antifibrotic effect in vivo.

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“…Osteoarthritis (OA) is one of the most prevalent chronic diseases [1], which affects more than 70% of people older than 50 years and its prevalence clearly increases with age until 70 years old [2]. It can affect any joint, but preferably affects the knee, hands, hip and spine [3]. Pain, stiffness and loss of functionality caused by OA have an important impact in the quality of life of patients [4,5].…”

Section: Introductionmentioning

confidence: 99%

The effectiveness of a web-based decision aid for patients with hip osteoarthritis: study protocol for a randomized controlled trial.

Perestelo‐Pérez¹,

Álvarez‐Pérez

Rivero‐Santana

et al. 2020

Preprint

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Background: Osteoarthritis (OA) is a health condition sensitive to patient’s preferences and values regarding the benefits and risks of the different treatment options. In this sense, patient decision aids (PtDA) can play an important role in helping patients to incorporate their values, needs and preferences into the decision-making process, thus improving Person-Centred Care. Previous research has focused almost exclusively on knee OA, and therefore the aim of this study is to develop and evaluate the effectiveness of a PtDA for patients with hip OA.Methods: The general design consists of two phases: 1) design a web-based PtDA for patients with hip OA, following the recommended procedures: systematic review of safety/effectiveness of treatments, and an iterative process of development with the help of an Advisory Committee composed of health professionals and patients; 2) To evaluate the impact of the PtDA on hip OA patients’ decision-making process related with their treatment. For that aim, a multicenter randomized controlled trial will be carried out with 124 patients with hip OA in Tenerife (Spain) comparing intervention or usual care.Discussion: PtDAs have been recommended as a useful and effective resource for improving PCC in many health conditions. The intervention is intended to empower patients by fostering their active participation during the decision-making process about their treatment, and by ensuring they make informed decisions congruent with their values and preferences. This study will contribute to the scientific knowledge about effectiveness of PtDAs in hip OA, in order to improve the quality of health care offered to these patients.Trial registration: ClinicalTrials.gob (NCT04241978). Registered on 24 January 2020.

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Osteoarthritis year in review 2019: epidemiology and therapy

Cited by 406 publications

References 40 publications

EGR1 Transcription Factor is a Multifaceted Regulator of Matrix Production in Tendons and Other Connective Tissues

EGR1 Transcription Factor is a Multifaceted Regulator of Matrix Production in Tendons and Other Connective Tissues

Proteoglycan-4 Regulates Fibroblast to Myofibroblast Transition and Expression of Fibrotic Genes in the Synovium

The effectiveness of a web-based decision aid for patients with hip osteoarthritis: study protocol for a randomized controlled trial.

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