Identification of differentially expressed microRNAs in knee anterior cruciate ligament tissues surgically removed from patients with osteoarthritis

Li, Bin; Bai, Lan; Shen, Peng; Sun, Yue; Chen, Zhizuo; Wen, Yu

doi:10.3892/ijmm.2017.3086

Cited by 38 publications

(32 citation statements)

References 48 publications

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“…In this regard, a set of miRNAs (e.g., let-7f-5p, miR-26b-5p and miR-146a-5p) was found to be upregulated in ACLs of OA patients compared with healthy individuals, while others were downregulated (e.g., miR-18a-3p, miR-138-5p, and miR-485-3p). Among others, the BMP2, TGFβ, and IL-6 genes were predicted as potential targets of these dysregulated miRNAs [128]. Hence, one can assume that a dysregulation of BMP family candidates involved in remodeling of joint cartilage, bone and ligaments by OA might also contribute to features of ligament degeneration.…”

Section: Candidate Signaling Pathways Involved In Ligament Degenermentioning

confidence: 99%

Intraarticular Ligament Degeneration Is Interrelated with Cartilage and Bone Destruction in Osteoarthritis

Schulze‐Tanzil

2019

Cells

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Osteoarthritis (OA) induces inflammation and degeneration of all joint components including cartilage, joint capsule, bone and bone marrow, and ligaments. Particularly intraarticular ligaments, which connect the articulating bones such as the anterior cruciate ligament (ACL) and meniscotibial ligaments, fixing the fibrocartilaginous menisci to the tibial bone, are prone to the inflamed joint milieu in OA. However, the pathogenesis of ligament degeneration on the cellular level, most likely triggered by OA associated inflammation, remains poorly understood. Hence, this review sheds light into the intimate interrelation between ligament degeneration, synovitis, joint cartilage degradation, and dysbalanced subchondral bone remodeling. Various features of ligament degeneration accompanying joint cartilage degradation have been reported including chondroid metaplasia, cyst formation, heterotopic ossification, and mucoid and fatty degenerations. The entheses of ligaments, fixing ligaments to the subchondral bone, possibly influence the localization of subchondral bone lesions. The transforming growth factor (TGF)β/bone morphogenetic (BMP) pathway could present a link between degeneration of the osteochondral unit and ligaments with misrouted stem cell differentiation as one likely reason for ligament degeneration, but less studied pathways such as complement activation could also contribute to inflammation. Facilitation of OA progression by changed biomechanics of degenerated ligaments should be addressed in more detail in the future.

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Section: Candidate Signaling Pathways Involved In Ligament Degenermentioning

confidence: 99%

Intraarticular Ligament Degeneration Is Interrelated with Cartilage and Bone Destruction in Osteoarthritis

Schulze‐Tanzil

2019

Cells

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“…To begin to elucidate the role that they play in the global changes observed in the ACL during OA and understand further the potential role of the ACL in arthritis, we undertook a non-biased approach small RNA sequencing of ACLs from OA knee joints and compared these to our control samples derived from non-OA knee joints. Whilst a study previously demonstrated DE miRNAs in ACL [20], this is the first time that, to our knowledge, small RNA sequencing has been used to interrogate both snoRNAs and miRNAs in an unbiased manner and we identified unique OA dependant signatures.…”

Section: Discussionmentioning

confidence: 80%

“…There is currently substantial interest in the area of epigenetic regulation in ageing, disease, and repair mechanisms in musculoskeletal tissues such as muscle [13,14], cartilage [15,16], tendon [17,18] and ligament [19,20]. Epigenetics is the study of changes in gene expression that do not derive from changes to the genetic code itself [21].…”

Section: Introductionmentioning

confidence: 99%

Small RNA signatures of the anterior cruciate ligament from patients with knee joint osteoarthritis

Kharaz

Fang²,

Welting

et al. 2020

Preprint

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The anterior cruciate ligaments are susceptible to degeneration, resulting in pain, reduced mobility and development of the degenerative joint disease osteoarthritis. There is currently a paucity of knowledge on how anterior cruciate ligament degeneration and disease can lead to osteoarthritis. Small non-coding RNAs (sncRNAs), such as microRNAs, and small nucleolar RNA, are important regulators of gene expression. We aimed to identify sncRNA profiles of human anterior cruciate ligaments to provide novel insights into their roles in osteoarthritis. RNA was extracted from the anterior cruciate ligaments of non-osteoarthritic knee joints (control) and end-stage osteoarthritis knee joints, used for small RNA sequencing and significantly differentially expressed sncRNAs defined. Bioinformatic analysis was undertaken on the differentially expressed miRNAs and their putative target mRNAs to investigate pathways and biological processes affected. Our analysis identified 184 sncRNA that were differentially expressed between control ACLs derived from osteoarthritic joints with a false discovery adjusted p value<0.05; 68 small nucleolar RNAs, 26 small nuclear RNAs and 90 microRNAs. We identified both novel and previously identified (miR-206, -101, -365 and -29b and -29c) osteoarthritis-related microRNAs and other sncRNAs (including SNORD74, SNORD114, SNORD72) differentially expressed in ligaments derived from osteoarthritic joints. Significant cellular functions deduced by the differentially expressed miRNAs included differentiation of muscle (P<0.001), inflammation (P<1.42E−10), proliferation of chondrocytes (P<0.03), fibrosis (P<0.001) and cell viability (P<0.03). Putative mRNAs were associated with the canonical pathways Hepatic Fibrosis Signalling (P<3.7E-32), and Osteoarthritis (P<2.2E−23). Biological processes included apoptosis (P<1.7E−85), fibrosis (P<1.2E−79), inflammation (P<3.4E−88), necrosis (P<7.2E−88) and angiogenesis (P<5.7E−101). SncRNAs are important regulators of anterior cruciate disease during osteoarthritis and may be used as therapeutic targets to prevent and manage anterior cruciate ligament disease and the resultant osteoarthritis.

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“…Data indicated that miRNAs are direct regulators for about one third of the genes via target binding [8]. Recently, miRNAs has also been shown to be involved in maintaining cartilage homeostasis in OA, as well as inflammatory response during development [9].…”

Section: Introductionmentioning

confidence: 99%

miR-200a/b relieves IL-1β-induced cell injury in knee articular chondrocytes ex-vivo by targeting fucosyltransferase 4 (FUT4)

Wei

Zhang

2020

Preprint

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Background: Osteoarthritis (OA) is a common subtype of arthritis with prevalence increase with age, and is characterized by the degeneration of articular cartilage. Chondrocytes play curial role in the formation of the articular cartilage. This work aimed to figure out the effect of miR-200a/b in chondrocytes of OA, as well as the underlying molecular mechanism. Methods: Cell viability, apoptosis, pro-inflammatory factors secretion, and matrix degradation were detected with cell counting kit-8 (CCK-8), flow cytometry, enzyme-linked immunosorbent assay (ELISA), and western blotting, separately. Expression of miR-200a/b and fucosyltransferase 4 (FUT4) was measured by RT-qPCR (RNA level) and western blot (protein level). The relationship between miR-200a/b and FUT4 was verified by dual-luciferase assay and RNA immunoprecipitation (RIP) assay. Results: Interleukin 1β (IL-1β) induced OA cell model in primary chondrocytes ex-vivo, as evidenced by cell viability inhibition, apoptosis rate promotion, and IL-6 and tumor necrosis factor α (TNF-α) resection enhancement, as well as Collegen 2a1 (Col2a1) and Aggrecan expression inhibition. Expression of miR-200a/b was downregulated in knee articular cartilage of OA patients and IL-1β-induced primary chondrocytes. miR-200a/b overexpression decreased IL-1β-induced cell injuries, which was further blocked by FUT4 upregulation. Mechanically, FUT4 was negatively regulated by miR-200a/b via target binding. Conclusion: miR-200a/b could alleviate IL-1β-induced chondrocyte injuries via targeting its downstream gene FUT4, suggesting that miR-200a/b-FUT4 axis might be a potential candidate to the treatment of OA.

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Identification of differentially expressed microRNAs in knee anterior cruciate ligament tissues surgically removed from patients with osteoarthritis

Cited by 38 publications

References 48 publications

Intraarticular Ligament Degeneration Is Interrelated with Cartilage and Bone Destruction in Osteoarthritis

Intraarticular Ligament Degeneration Is Interrelated with Cartilage and Bone Destruction in Osteoarthritis

Small RNA signatures of the anterior cruciate ligament from patients with knee joint osteoarthritis

miR-200a/b relieves IL-1β-induced cell injury in knee articular chondrocytes ex-vivo by targeting fucosyltransferase 4 (FUT4)

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