Regulation of inflammatory and catabolic responses to IL-1β in rat articular chondrocytes by microRNAs miR-122 and miR-451

Scott, Kayla M.; Cohen, David J.; Hays, Marguerite T.; Grinstaff, Mark W.; Lawson, Thomas; Snyder, Brian D.; Boyan, Barbara D.; Schwartz, Zvi

doi:10.1016/j.joca.2020.09.004

Cited by 16 publications

(24 citation statements)

References 46 publications

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“…Previous data showed that transfection with miR‐122 was able to inhibit the IL‐1β‐stimulated increase in MMP‐13 and PGE2 while transfection with miR‐451 exacerbated the production of these two molecules 20 . However the effects of these microRNA on TNF‐α‐dependent MMP‐13 or PGE2 have not been tested.…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, miR‐122 appears to target FOXO3 which modulates the WNT/β‐catenin signaling pathway, 39–42 which may explain miR‐122's protective role in IL‐1β‐ and TNF‐α‐stimulated cultures. miR‐451 transfection exacerbates the production of MMP‐13 and PGE2 in the presence of IL‐1β stimulation, but has no inflammatory signaling in the absence of IL‐1β 20 . Furthermore, miR‐451 had no effect in TNF‐α‐stimulated cultures, indicating it is targeting a specific branch or inhibitor in the IL‐1β signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…rArCs were isolated using a previously established protocol 20,22,23 . All animal procedures were approved by Virginia Commonwealth University's Institutional Animal Care and Use Committee.…”

Section: Methodsmentioning

confidence: 99%

“…The concentration of the miRNAs, transfection efficiency, and cytotoxicity studies were all performed and previously established. Cell transfection was performed using this previously established protocol 20 . Briefly, at 60% confluence, rArCs were transfected for 24 h with 14.5 nM of mirVana miRNA mimic rno‐miR‐122‐5p or rno‐miR‐451‐5p (Thermo Fisher Scientific) using 0.2% lipofectamine RNAimax (Lipo; Life Technologies) in antibiotic‐free DMEM supplemented with 10% FBS 24 .…”

Section: Methodsmentioning

confidence: 99%

“…16 Increasing evidence suggests that disease pathologies can be enhanced or inhibited through microRNA (miR) regulation, 17,18 and specific microRNAs such as miR-17-5p, miR-21-5p, miR-101, and miR-451a are elevated in OA. [19][20][21] Recent findings determined that miR-122-5p prevents the associated increase in MMP-13, PGE 2 , and other cytokines implicated in OA in primary rat articular chondrocytes (rArCs) upon stimulation with IL-1β. 20 Conversely, miR-451-5p exacerbated the increase of MMP-13, PGE 2 , and numerous other cytokines, but only in the presence of IL-1β.…”

Section: Introductionmentioning

confidence: 99%

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miR‐122 and the WNT/β‐catenin pathway inhibit effects of both interleukin‐1β and tumor necrosis factor‐α in articular chondrocytes in vitro

Scott

Cohen

Boyan

et al. 2022

J of Cellular Biochemistry

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Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and WNT/β-catenin signaling cause dysregulation of rat primary articular chondrocytes (rArCs), resulting in cartilage extracellular matrix destruction and osteoarthritis (OA) progression. microRNA (miR) miR-122 represses these effects whereas miR-451 exacerbates IL-1β-stimulated matrix metalloproteinase-13 (MMP-13) and prostaglandin E2 (PGE2) production. The goals of this study were to evaluate crosstalk between these signaling pathways and determine if miR-122 and miR-451 exert their protective/destructive effects through these pathways in an in vitro model of OA. Primary rArCs were treated with IL-1β or TNF-α for 24 h and total DNA, MMP-13, and PGE2, as well as expression levels of miR-122 and miR-451 were measured. After 24-h transfection with miR-122, miR-451, miR-122-inhibitor, or miR-451-inhibitor, rArCs were treated with or without TNF-α for 24 h; total DNA, MMP-13, and PGE2 were measured.Similarly, cells were treated with WNT-agonist lithium chloride (LiCl), WNTantagonist XAV-939 (XAV), or PKF-118-310 (PKF) with and without IL-1β or TNF-α stimulation. Both IL-1β and TNF-α-stimulation increased MMP-13 and PGE2 production. Transfection with miR-122 prevented TNF-α-stimulated increases in MMP-13 and PGE2 whereas transfection with miR-451 did not change these levels. No differences were found in MMP-13 or PGE2 production with miR-122 or miR-451 inhibitors. LiCl treatment decreased PGE2 production in cultures treated with TNF-α, but not MMP-13. XAV increased TNF-α-stimulated increases in PGE2 but not MMP-13. LiCl reduced IL-1β-stimulated increases in MMP-13 and PGE2. XAV and PKF increased IL-1β-stimulated increases in MMP-13 and PGE2. In this in vitro OA model, miR-122 protects against both IL-1β and TNF-α stimulated increases in MMP-13 and PGE2 production. miR-451 does not act through the TNF-α pathway. The WNT/β-catenin pathway regulates the effects of IL-1β and TNF-α

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%