000			02965nam a22003377a 4500
008			240723s20242024 xxu||||| |||| 00| 0 eng d
022			_a2701-0198
040			_aOvid MEDLINE(R)
099			_a38419396
245			_aExploring the Impact of TLR-2 Signaling on miRNA Dysregulation in Intervertebral Disc Degeneration.
251			_aAdvances in Biology Online. :e2300581, 2024 Feb 28
252			_aadv. biol. :e2300581, 2024 Feb 28
253			_aAdvanced biology
260			_c2024
260			_p2024 Feb 28
265			_saheadofprint
265			_tPublisher
266			_d2024-07-23
520			_aToll-like receptors (TLRs) are key mediators of inflammation in intervertebral disc (IVD) degeneration. TLR-2 activation contributes to the degenerative process by increasing the expression of extracellular matrix-degrading enzymes, pro-inflammatory cytokines, and neurotrophins. As potent post-transcriptional regulators, microRNAs can modulate intracellular mechanisms, and their dysregulation is known to contribute to numerous pathologies. This study aims to investigate the impact of TLR-2 signaling on miRNA dysregulation in the context of IVD degeneration. Small-RNA sequencing of degenerated IVD cells shows the dysregulation of ten miRNAs following TLR-2 activation by PAM2CSK4. The miR-155-5p is most significantly upregulated in degenerated and non-degenerated annulus fibrosus and nucleus pulposus cells. Sequence-based target and pathway prediction shows the involvement of miR-155-5p in inflammation- and cell fate-related pathways and TLR-2-induced miR-155-5p expression leads to the downregulation of its target c-FOS. Furthermore, changes specific to the activation of TLR-2 through fragmented fibronectin are seen in miR-484 and miR-487. Lastly, miR-100-3p, miR-320b, and miR-181a-3p expression exhibit degeneration-dependent changes. These results show that TLR-2 signaling leads to the dysregulation of miRNAs in IVD cells as well as their possible downstream effects on inflammation and degeneration. The identified miRNAs provide important opportunities as potential therapeutic targets for IVD degeneration and low back pain. Copyright © 2024 The Authors. Advanced Biology published by Wiley-VCH GmbH.
546			_aEnglish
650			_zAutomated
650			_aIN PROCESS -- NOT YET INDEXED
651			_aMedStar Washington Hospital Center
656			_aOrthopedic Surgery
657			_aJournal Article
700			_aMesfin, Addisu _bMWHC
790			_aCazzanelli P, Lamoca M, Hausmann ON, Mesfin A, Puvanesarajah V, Hitzl W, Haglund L, Wuertz-Kozak K
856			_uhttps://dx.doi.org/10.1002/adbi.202300581 _zhttps://dx.doi.org/10.1002/adbi.202300581
858			_yCazzanelli, Petra _uhttps://orcid.org/0009-0007-3114-951XI - Wuertz-Kozak, Karin _uhttps://orcid.org/0000-0002-3281-4629 _zhttps://orcid.org/0009-0007-3114-951XI - Wuertz-Kozak, Karin _zhttps://orcid.org/0000-0002-3281-4629
942			_cART _dArticle
999			_c14223 _d14223