Publication:
Can transcription factors in the intervertebral disc of lopinavir/ritonavir prevent degeneration in the nucleus pulposus by mediating the regulation of inflammation through signaling pathways?

dc.contributor.coauthorYılmaz, I.
dc.contributor.coauthorAkalan, H.
dc.contributor.coauthorKaraarslan, N.
dc.contributor.coauthorYaşar Şirin, D.
dc.contributor.coauthorKaplan, N.
dc.contributor.coauthorDoğan, M.
dc.contributor.coauthorÖzbek, H.
dc.contributor.departmentSchool of Medicine
dc.contributor.kuauthorAteş, Özkan
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-11-09T13:09:30Z
dc.date.issued2022
dc.description.abstractObjective: this study was conducted to examine whether lopinavir/ritonavir (Lop/r), an HIV protease inhibitor, can improve disc physiology and slow down intervertebral disc (IVD) degeneration through in vitro experimental methods, as well as whether it can suppress inflammation with interleukin-1 beta (IL-1?) and sex-determining region Y (SRY) protein-related high-mobility group box genes-9 (SOX9) through hypoxia-inducible factor 1-alpha (HIF-1?) and the nuclear factor kappa B (NF-?B) signaling pathway. The aim was to investigate whether Lop/r application is toxic to IVD cells and the microenvironment simultaneously. Patients and methods: human primary cell cultures were prepared using herniated IVD tissues obtained from patients with lumbar disc hernia who were unresponsive to conservative and medical treatment, and thereby, were operated on. The untreated culture samples served as control group, and the samples treated with Lop/r served as study group. Microscopic evaluations were performed simultaneously using fluorescent and supravital dyes in all groups. In addition to cell viability, toxicity, and proliferation analysis through a commercial kit, IL-1?, SOX9, HIF-1?, and NF-?B protein expressions were evaluated using Western blotting. In the statistical comparison of the obtained data, an alpha value less than 0.05 was considered significant. Results: cell proliferation decreased in the Lop/r group, but no cell death was observed (p < 0.05). Moreover, at the end of 72 hours after Lop/r application, IL-1? and NF-kB protein expressions decreased by 40% and 52%, respectively, while HIF-1? and SOX9 protein expressions increased by 4% and 59%, respectively (p< 0.05). Conclusion: although these data were obtained from an in vitro experimental study, it is believed that these findings could make significant contributions to the pharmaco-regenerative treatment modalities of IVD degeneration. Lop/r suppresses the IL-1? and NF-?B and induces SOX9 and HIF-1?, since these signaling pathways may be related to human IVD degeneration.
dc.description.fulltextYES
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue18
dc.description.openaccessYES
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipN/A
dc.description.versionPublisher version
dc.description.volume26
dc.identifier.doi10.26355/eurrev_202209_29788
dc.identifier.embargoNO
dc.identifier.filenameinventorynoIR03922
dc.identifier.issn1128-3602
dc.identifier.quartileQ2
dc.identifier.scopus2-s2.0-85139572996
dc.identifier.urihttps://hdl.handle.net/20.500.14288/2760
dc.keywordsAutophagy
dc.keywordsDisc degeneration
dc.keywordsHypoxia
dc.keywordsInflammation
dc.keywordsLop/r
dc.keywordsSOX9
dc.language.isoeng
dc.publisherVerduci Editore
dc.relation.grantnoNA
dc.relation.ispartofEuropean Review for Medical and Pharmacological Sciences
dc.relation.urihttp://cdm21054.contentdm.oclc.org/cdm/ref/collection/IR/id/10788
dc.subjectMedicine
dc.titleCan transcription factors in the intervertebral disc of lopinavir/ritonavir prevent degeneration in the nucleus pulposus by mediating the regulation of inflammation through signaling pathways?
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorAteş, Özkan
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit2School of Medicine
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relation.isOrgUnitOfPublication.latestForDiscoveryd02929e1-2a70-44f0-ae17-7819f587bedd
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