Dual and Opposing Regulation of MMP1 and MMP13 by Both Arms of miR-675 in Human Articular Chondrocytes

doi:10.33594/000000128

Cited by 7 publications

(5 citation statements)

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“…Of all differentially expressed miRNA sequences 40 were 3p strands, 36 were 5p strands and 24 of the 76 sequences were isomiRs. Several of the canonical miRNAs upregulated in ACs, such as miR-675-3p and 5p, miR-335-5p, miR-582-5p and 3p, miR-9-5p, miR-136-3p and miR 495-3p are known to be involved in cartilage biogenesis and disease ( Tomé et al, 2011 ; Díaz-Prado et al, 2012 ; Chen et al, 2017 ; Chen et al, 2018 ; Zhong G. et al, 2019 ; Chen et al, 2019 ; Seidl and Murphy, 2019 ; Wang et al, 2019 ; Chen et al, 2020 ; Shen et al, 2020 ; Zhang et al, 2021 ). Of the highest differentially expressed canonical miRNAs in MSCs miR-10a-5p, miR-181b, miR-181a, miR-135b-5p and miR-218-5p are known to be involved in osteogenesis, cartilage hypertrophy and degeneration and OA ( Bhushan et al, 2013 ; Song et al, 2013 ; Gabler et al, 2015 ; Nakamura et al, 2016 ; Lu et al, 2017 ; Ma et al, 2019 ; Yin et al, 2019 ; Li et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…For instance overexpression of miR-675-3p has been found to inhibit apoptosis and cartilage matrix degradation and promote cell proliferation in human chondrocytes ( Shen et al, 2020 ). The 3′ arm of miR-675 was found to be the only functional arm of miR-675 in ACs, and was found to downregulate cartilage degrading enzymes matrix metalloprotein 1 (MMP1) and MMP13 ( Seidl and Murphy, 2019 ). MiR-335-5p has been shown to inhibit adipogenic and osteogenic differentiation of hMSCs ( Tomé et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

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Comparison between articular chondrocytes and mesenchymal stromal cells for the production of articular cartilage implants

Frerker

Karlsen

Stensland

et al. 2023

Front. Bioeng. Biotechnol.

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Focal lesions of articular cartilage give rise to pain and reduced joint function and may, if left untreated, lead to osteoarthritis. Implantation of in vitro generated, scaffold-free autologous cartilage discs may represent the best treatment option. Here we compare articular chondrocytes (ACs) and bone marrow-derived mesenchymal stromal cells (MSCs) for their ability to make scaffold-free cartilage discs. Articular chondrocytes produced more extracellular matrix per seeded cell than mesenchymal stromal cells. Quantitative proteomics analysis showed that articular chondrocyte discs contained more articular cartilage proteins, while mesenchymal stromal cell discs had more proteins associated with cartilage hypertrophy and bone formation. Sequencing analysis revealed more microRNAs associated with normal cartilage in articular chondrocyte discs, and large-scale target predictions, performed for the first time for in vitro chondrogenesis, suggested that differential expression of microRNAs in the two disc types were important mechanisms behind differential synthesis of proteins. We conclude that articular chondrocytes should be preferred over mesenchymal stromal cells for tissue engineering of articular cartilage.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparison between articular chondrocytes and mesenchymal stromal cells for the production of articular cartilage implants

Frerker

Karlsen

Stensland

et al. 2023

Front. Bioeng. Biotechnol.

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“…miR-134 was found to regulate MMP3 expression by Chen [36]. Similarly, Seidl CI et al [37] found that miR-675 could regulate MMP13 expression, but it has also been found that miR-411 could also regulate MMP13 expression by expression to regulate tissue repair [38].…”

Section: Resultsmentioning

confidence: 99%

Differential expression of related molecules after acute injury of rabbits’ anterior cruciate ligament and medial collateral ligament

Wen¹,

Han²,

Gu³

et al. 2021

Preprint

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Objective: This study aimed to assay expression of the mRNA and proteins for injuring- and angiogenesis-associated molecules at 3 days, 1week, 2weeks, 4weeks and 6 weeks after anterior cruciate ligament or medial collateral ligament injury in male New Zealand White rabbits.Methods: Models similar to those of clinical patients were used to establish acute partial injuries of the anterior cruciate ligament and medial collateral ligament at 3 days, 1 week, 2 weeks, 4 weeks and 6 weeks and normal control groups. Molecular biological changes in male rabbits were detected at different time points after anterior cruciate ligament and medial collateral ligament injury by H&E staining, reverse transcriptase chain reaction and westren blotting.Results: Marked differences were found in the postinjury changes in gene levels and proteins in the anterior cruciate ligament compared to the medial collateral ligament. There was no increase in mRNA expression of TIMP3, TGF-βand PRG4 in the injured anterior cruciate ligament at any time point. However, the levels of these genes tended to increase in the injured medial collateral ligament. In contrast, MMP-13 mRNA levels were significantly increased in the injured anterior cruciate ligament, but not in the medial collateral ligament. Furthermore, vascular endothelial growth factor decreased following injury to both the anterior cruciate ligament and medial collateral ligament, with the difference being a slight decrease in the medial collateral ligament and a significant decrease in the anterior cruciate ligament. Similarly, protein blots showed higher protein expression of type I and type III collagen in the injured medial collateral ligament than in the anterior cruciate ligament.Conclusion: The results show that there were drastic differences in angiogenesis, collagen and Matrix metalloproteinases after anterior cruciate ligament and medial collateral ligament injury. It can be found that the repair ability of the anterior cruciate ligament and medial collateral ligament after injury may be related to the differences in molecular expression.

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“…IL21 was found to suppress HC-a chondrocyte proliferation, promote apoptosis, and downregulate miR-361-5p. The restoration of HC-a cell functions was noted with increased miR-361-5p, implicating MAP3K9 as a target gene, and revealing a role for miR-361-5p in regulating MMP1, a collagen-degrading enzyme [ 32 ]. The ERK1/2/NF-κB signaling pathway’s involvement in MMP expression was confirmed using specific agonists.…”

Section: Discussionmentioning

confidence: 99%

IL21 inhibits miR-361-5p to promote MAP3K9 and further aggravate the progression of shoulder arthritis

Hao,

Lin,

et al. 2024

Aging

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: Objective: This research aimed to explore IL-21/miR-361-5p/MAP3K9 expression in shoulder arthritis and identify its regulatory pathways. Methods: We established a rat shoulder arthritis model, then quantified IL21 and miR-361-5p in synovial fluid using ELISA and monitored the arthritis development. Additionally, IL21’s effect on miR-361-5p levels in cultured human chondrocytes (HC-a) was assessed. Chondrocyte cell cycle status and apoptosis were measured via flow cytometry. Interactions between miR-361-5p and MAP3K9 were confirmed through dual-luciferase reporting and bioinformatic scrutiny. Protein levels of MAP3K9, p-ERK1/2, p-NF-κB, MMP1, and MMP9 were analyzed by Western blots. Results: IL21 levels were elevated, while miR-361-5p was reduced in the synovial fluid from arthritic rats compared to healthy rats. IL21 was shown to suppress miR-361-5p in chondrocytes leading to hindered cell proliferation and increased apoptosis. Western blots indicated that miR-361-5p curbed MAP3K9 expression, reducing MMP activity by attenuating the ERK1/2/NF-κB pathway in chondrocytes. Conclusion: IL21 upregulation and miR-361-5p downregulation characterize shoulder arthritis, resulting in MAP3K9 overexpression. This chain of molecular events boosts MMP expression in chondrocytes and exacerbates the condition’s progression.

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Dual and Opposing Regulation of MMP1 and MMP13 by Both Arms of miR-675 in Human Articular Chondrocytes

Abstract: This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

Cited by 7 publications

References 46 publications

Comparison between articular chondrocytes and mesenchymal stromal cells for the production of articular cartilage implants

Comparison between articular chondrocytes and mesenchymal stromal cells for the production of articular cartilage implants

Differential expression of related molecules after acute injury of rabbits’ anterior cruciate ligament and medial collateral ligament

IL21 inhibits miR-361-5p to promote MAP3K9 and further aggravate the progression of shoulder arthritis

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