Aging aggravates intervertebral disc degeneration by regulating transcription factors toward chondrogenesis

dc.contributor.authorSilva, Matthew J.
dc.contributor.authorHolguin, Nilsson
dc.contributor.departmentAnatomy and Cell Biology, School of Medicineen_US
dc.date.accessioned2022-05-24T17:00:38Z
dc.date.available2022-05-24T17:00:38Z
dc.date.issued2020-02
dc.description.abstractOsterix is a critical transcription factor of mesenchymal stem cell fate, where its loss or loss of Wnt signaling diverts differentiation to a chondrocytic lineage. Intervertebral disc (IVD) degeneration activates the differentiation of prehypertrophic chondrocyte-like cells and inactivates Wnt signaling, but its interactive role with osterix is unclear. First, compared to young-adult (5 mo), mechanical compression of old (18 mo) IVD induced greater IVD degeneration. Aging (5 vs 12 mo) and/or compression reduced the transcription of osterix and notochordal marker T by 40-75%. Compression elevated the transcription of hypertrophic chondrocyte marker MMP13 and pre-osterix transcription factor RUNX2, but less so in 12 mo IVD. Next, using an Ai9/td reporter and immunohistochemical staining, annulus fibrosus and nucleus pulposus cells of young-adult IVD expressed osterix, but aging and compression reduced its expression. Lastly, in vivo LRP5-deficiency in osterix-expressing cells inactivated Wnt signaling in the nucleus pulposus by 95%, degenerated the IVD to levels similar to aging and compression, reduced the biomechanical properties by 45-70%, and reduced the transcription of osterix, notochordal markers and chondrocytic markers by 60-80%. Overall, these data indicate that age-related inactivation of Wnt signaling in osterix-expressing cells may limit regeneration by depleting the progenitors and attenuating the expansion of chondrocyte-like cells.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationSilva MJ, Holguin N. Aging aggravates intervertebral disc degeneration by regulating transcription factors toward chondrogenesis. FASEB J. 2020;34(2):1970-1982. doi:10.1096/fj.201902109Ren_US
dc.identifier.urihttps://hdl.handle.net/1805/29134
dc.language.isoen_USen_US
dc.publisherWileyen_US
dc.relation.isversionof10.1096/fj.201902109Ren_US
dc.relation.journalFASEB Journalen_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subjectWnt/β-catenin/LRPsen_US
dc.subjectBiomechanicsen_US
dc.subjectGenetic animal modelsen_US
dc.subjectOsterixen_US
dc.titleAging aggravates intervertebral disc degeneration by regulating transcription factors toward chondrogenesisen_US
dc.typeArticleen_US
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