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Abstract
Background: Osteoarthritis (OA) is an inflammatory joint disorder with high incidence rates. Long non-coding RNAs (LncRNAs) influence OA development.
Objectives: In this research, we attempt to figure out the functions of lncRNA BLACAT1 in human articular chondrocyte (HAC) apoptosis and extracellular matrix (ECM) degradation in OA.
Methods: Interleukin (IL)-1β was employed to induce HAC damage. Cell viability and apoptosis were detected, with expression patterns of lncRNA BLACAT1, miR-149-5p, and HMGCR, and levels of Caspase-3, Caspase-9, BAX, Bcl-2, COL2A1, and SOX9 determined. Then, lncRNA BLACAT1 was silenced in IL-1β-treated HACs to analyze its role in HAC damage. The target relations of lncRNA BLACAT1 and miR-149-5p and miR-149-5p and HMGCR were verified. In addition, combined experiments were performed as a miR-149-5p inhibitor or HMGCR overexpression was injected into cells with lncRNA BLACAT1 silencing.
Results: In IL-1β-treated HACs, lncRNA BLACAT1 and HMGCR were overexpressed while miR- 149-5p was poorly expressed, along with reduced cell viability, enhanced apoptosis, elevated Caspase-3 and Caspase-9 activities, increased BAX level, decreased Bcl-2 level, and declined levels of COL2A1 and SOX9, which were reversed by lncRNA BLACAT1 silencing. LncRNA BLACAT1 targeted miR-149-5p, and miR-149-5p targeted HMGCR. miR-149-5p knockout or HMGCR overexpression annulled the inhibitory role of lncRNA BLACAT1 silencing in HAC apoptosis and ECM degradation.
Conclusion: LncRNA BLACAT1 was overexpressed in IL-1β-treated HACs, and the lncRNA BLACAT1/miR-149-5p/HMGCR ceRNA network promoted HAC apoptosis and ECM degradation.
Keywords: Osteoarthritis, articular chondrocytes, apoptosis, IL-1β, extracellular matrix, LncRNA BLACAT1, miR-149-5p, HMGCR.
[http://dx.doi.org/10.1016/j.fcl.2013.06.001] [PMID: 24008208]
[http://dx.doi.org/10.1016/j.joca.2018.11.001] [PMID: 30453055]
[http://dx.doi.org/10.3390/medicina56110614] [PMID: 33207632]
[PMID: 30222846]
[http://dx.doi.org/10.3390/ijms161125943] [PMID: 26528972]
[http://dx.doi.org/10.1186/s13287-019-1458-8] [PMID: 31753016]
[PMID: 32271407]
[http://dx.doi.org/10.1111/os.12690] [PMID: 32436304]
[PMID: 32141427]
[http://dx.doi.org/10.1007/s11596-016-1645-0] [PMID: 27752896]
[http://dx.doi.org/10.3389/fphar.2019.00947]
[http://dx.doi.org/10.1016/j.bbrc.2020.04.044] [PMID: 32336544]
[http://dx.doi.org/10.1093/bioinformatics/bty085] [PMID: 29462250]
[http://dx.doi.org/10.1093/nar/gkt1248] [PMID: 24297251]
[http://dx.doi.org/10.7554/eLife.05005] [PMID: 26267216]
[http://dx.doi.org/10.1093/nar/gkz757] [PMID: 31504780]
[http://dx.doi.org/10.1093/humupd/dmz029] [PMID: 31647106]
[http://dx.doi.org/10.3390/ijms160920560] [PMID: 26334269]
[http://dx.doi.org/10.2147/CMAR.S258178]
[http://dx.doi.org/10.1371/journal.pone.0035753] [PMID: 22662110]
[PMID: 30569118]
[http://dx.doi.org/10.1111/febs.14818] [PMID: 30908868]
[http://dx.doi.org/10.1016/j.jbspin.2016.09.006] [PMID: 27919571]
[http://dx.doi.org/10.1097/CM9.0000000000000755] [PMID: 32187055]
[http://dx.doi.org/10.2147/OTT.S261461]
[http://dx.doi.org/10.1016/j.micpath.2019.103892] [PMID: 31778755]
[http://dx.doi.org/10.1076/apab.105.2.125.12927] [PMID: 9296841]
[http://dx.doi.org/10.1097/01.blo.0000144478.51284.f3] [PMID: 15480054]
[http://dx.doi.org/10.1016/j.biopha.2019.109708] [PMID: 31918279]
[http://dx.doi.org/10.1016/j.ejphar.2019.172737]
[http://dx.doi.org/10.18632/aging.203201] [PMID: 34198264]
[http://dx.doi.org/10.2337/db16-0592] [PMID: 27737950]
[http://dx.doi.org/10.1093/jnen/nlaa006] [PMID: 32100014]