{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:31:21Z","timestamp":1780536681726,"version":"3.54.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T00:00:00Z","timestamp":1698192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>The pain in patients with Modic type 1 changes (MC1) is often due to vertebral body endplate pain, which is linked to abnormal neurite outgrowth in the vertebral body and adjacent endplate. The aim of this study was to understand the role of MC1 bone marrow stromal cells (BMSCs) in neurite outgrowth. BMSCs can produce neurotrophic factors, which have been shown to be pro-fibrotic in MC1, and expand in the perivascular space where sensory vertebral nerves are located. The study involved the exploration of the BMSC transcriptome in MC1, co-culture of MC1 BMSCs with the neuroblastoma cell line SH-SY5Y, analysis of supernatant cytokines, and analysis of gene expression changes in co-cultured SH-SY5Y. Transcriptomic analysis revealed upregulated brain-derived neurotrophic factor (BDNF) signaling-related pathways. Co-cultures of MC1 BMSCs with SH-SY5Y cells resulted in increased neurite sprouting compared to co-cultures with control BMSCs. The concentration of BDNF and other cytokines supporting neuron growth was increased in MC1 vs. control BMSC co-culture supernatants. Taken together, these findings show that MC1 BMSCs provide strong pro-neurotrophic cues to nearby neurons and could be a relevant disease-modifying treatment target.<\/jats:p>","DOI":"10.3389\/fcell.2023.1286280","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T10:20:44Z","timestamp":1698229244000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Bone marrow stromal cells in Modic type 1 changes promote neurite outgrowth"],"prefix":"10.3389","volume":"11","author":[{"given":"Tamara","family":"Mengis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Herger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Heggli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Devan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Miguel","family":"Spirig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph J.","family":"Laux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Brunner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazda","family":"Farshad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Distler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Dudli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1097\/00002517-199812000-00013","article-title":"Innervation of the human vertebral body: a histologic study","volume":"11","author":"Antonacci","year":"1998","journal-title":"J. Spinal Disord."},{"key":"B2","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1111\/j.1469-7580.2010.01332.x","article-title":"Innervation patterns of PGP 9.5-positive nerve fibers within the human lumbar vertebra","volume":"218","author":"Bailey","year":"2011","journal-title":"J. Anat."},{"key":"B3","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1002\/ejp.838","article-title":"Neuropathic low back pain in clinical practice","volume":"20","author":"Baron","year":"2016","journal-title":"Eur. J. Pain (United Kingdom)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1093\/biomet\/93.3.491","article-title":"Adaptive linear step-up procedures that control the false discovery rate","volume":"93","author":"Benjamini","year":"2006","journal-title":"Biometrika"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e45052","DOI":"10.1371\/journal.pone.0045052","article-title":"Aging effect on neurotrophic activity of human mesenchymal stem cells","volume":"7","author":"Brohlin","year":"2012","journal-title":"PLoS ONE"},{"key":"B6","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1302\/0301-620x.79b1.6814","article-title":"Sensory and sympathetic innervation of the vertebral endplate in patients with degenerative disc disease","volume":"79","author":"Brown","year":"1997","journal-title":"J. Bone Jt. Surg. Br."},{"key":"B7","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1002\/aja.1001230206","article-title":"The innervation of the bone marrow in laboratory animals","volume":"123","author":"Calvo","year":"1968","journal-title":"Am. J. Anat."},{"key":"B8","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/nature03875","article-title":"Common mechanisms of nerve and blood vessel wiring","volume":"436","author":"Carmeliet","year":"2005","journal-title":"Nature"},{"key":"B9","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/s1529-9430(02)00455-2","article-title":"Substance P\u2013containing nerves within the human vertebral body","volume":"3","author":"Christian","year":"2003","journal-title":"Spine J."},{"key":"B10","doi-asserted-by":"publisher","first-page":"S63","DOI":"10.1093\/pm\/pnac081","article-title":"Vertebrogenic pain: a paradigm shift in diagnosis and treatment of axial low back pain","volume":"23","author":"Conger","year":"2022","journal-title":"Pain Med. (United States)"},{"key":"B11","doi-asserted-by":"publisher","first-page":"3723","DOI":"10.1007\/s00586-016-4459-7","article-title":"Pathobiology of modic changes","volume":"25","author":"Dudli","year":"2016","journal-title":"Eur. Spine J."},{"key":"B12","doi-asserted-by":"publisher","first-page":"100287","DOI":"10.1016\/j.ocarto.2022.100287","article-title":"CD90-positive stromal cells associate with inflammatory and fibrotic changes in modic changes","volume":"4","author":"Dudli","year":"2022","journal-title":"Osteoarthr. Cartil. Open"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1007\/s00586-017-4955-4","article-title":"ISSLS PRIZE IN BASIC SCIENCE 2017: intervertebral disc\/bone marrow cross-talk with Modic changes","volume":"26","author":"Dudli","year":"2017","journal-title":"Eur. Spine J."},{"key":"B14","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.spinee.2013.06.075","article-title":"Innervation of pathologies in the lumbar vertebral end plate and intervertebral disc","volume":"14","author":"Fields","year":"2014","journal-title":"Spine J."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1007\/s00586-020-06448-x","article-title":"Long-term outcomes following intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: 5-year treatment arm results from a prospective randomized double-blind sham-controlled multi-center study","volume":"29","author":"Fischgrund","year":"2020","journal-title":"Eur. Spine J."},{"key":"B16","doi-asserted-by":"publisher","first-page":"15062","DOI":"10.3390\/ijms232315062","article-title":"Investigating SH-SY5Y neuroblastoma cell surfaceome as a model for neuronal-targeted novel therapeutic modalities","volume":"23","author":"Gangras","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"610887","DOI":"10.3389\/fcell.2021.610887","article-title":"Expression of Drosophila matrix metalloproteinases in cultured cell lines alters neural and glial cell morphology","volume":"9","author":"Hearst","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"648","DOI":"10.22203\/eCM.v041a42","article-title":"Pro-fibrotic phenotype of bone marrow stromal cells in modic type 1 changes","volume":"41","author":"Heggli","year":"2021","journal-title":"Eur. Cells Mater."},{"key":"B19","first-page":"65","article-title":"A simple sequentially rejective multiple test procedure","volume":"6","author":"Holm","year":"1979","journal-title":"Scand. J. Statistics"},{"key":"B20","doi-asserted-by":"publisher","first-page":"118737","DOI":"10.1016\/j.bbamcr.2020.118737","article-title":"Brain-derived neurotrophic factor (BDNF) promotes molecular polarization and differentiation of immature neuroblastoma cells into definitive neurons","volume":"1867","author":"Hromadkova","year":"2020","journal-title":"Biochimica Biophysica Acta (BBA) - Mol. Cell Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1007\/s00586-008-0770-2","article-title":"Vertebral endplate signal changes (Modic change): a systematic literature review of prevalence and association with non-specific low back pain","volume":"17","author":"Jensen","year":"2008","journal-title":"Eur. Spine J."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.3390\/ijms21041483","article-title":"Lumbar degenerative disease part 1: anatomy and pathophysiology of intervertebral discogenic pain and radiofrequency ablation of basivertebral and sinuvertebral nerve treatment for chronic discogenic back pain: a prospective case series and review of literature","volume":"21","author":"Kim","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.3892\/etm.2014.2033","article-title":"Brain-derived neurotrophic factor exerts neuroprotective actions against amyloid \u03b2-induced apoptosis in neuroblastoma cells","volume":"8","author":"Kim","year":"2014","journal-title":"Exp. Ther. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.1128\/mcb.00008-13","article-title":"Brain-derived neurotrophic factor induces matrix metalloproteinase 9 expression in neurons via the serum response factor\/C-Fos pathway","volume":"33","author":"Kuzniewska","year":"2013","journal-title":"Mol. Cell. Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"W199","DOI":"10.1093\/nar\/gkz401","article-title":"WebGestalt 2019: gene set analysis toolkit with revamped UIs and APIs","volume":"47","author":"Liao","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1055\/s-0033-1347298","article-title":"The role of the vertebral end plate in low back pain","volume":"3","author":"Lotz","year":"2013","journal-title":"Glob. Spine J."},{"key":"B27","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/0092-8674(93)80064-l","article-title":"Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones","volume":"75","author":"Luo","year":"1993","journal-title":"Cell"},{"key":"B28","doi-asserted-by":"publisher","first-page":"16630","DOI":"10.1038\/s41598-018-34933-3","article-title":"Strong association between vertebral endplate defect and Modic change in the general population","volume":"8","author":"M\u00e4\u00e4tt\u00e4","year":"2018","journal-title":"Sci. Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1148\/radiology.166.1.3336678","article-title":"Degenerative disk disease: assessment of changes in vertebral body marrow with MR imaging","volume":"166","author":"Modic","year":"1988","journal-title":"Radiology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.euprot.2017.06.001","article-title":"Quantitative proteomic analysis identifies proteins and pathways related to neuronal development in differentiated SH-SY5Y neuroblastoma cells","volume":"16","author":"Murillo","year":"2017","journal-title":"EuPA Open Proteomics"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1097\/01.brs.0000215027.87102.7c","article-title":"Tumor necrosis factor-immunoreactive cells and PGP 9.5-immunoreactive nerve fibers in vertebral endplates of patients with discogenic low back pain and modic type 1 or type 2 changes on MRI","volume":"31","author":"Ohtori","year":"2009","journal-title":"SPINE"},{"key":"B32","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1007\/s10571-016-0403-y","article-title":"Transcriptomic profiling discloses molecular and cellular events related to neuronal differentiation in SH-SY5Y neuroblastoma cells","volume":"37","author":"Pezzini","year":"2017","journal-title":"Cell. Mol. Neurobiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1186\/s13287-019-1517-1","article-title":"Bone marrow-derived neural crest precursors improve nerve defect repair partially through secreted trophic factors","volume":"10","author":"Shi","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"B34","doi-asserted-by":"publisher","first-page":"53193","DOI":"10.3791\/53193","article-title":"Differentiation of the SH-SY5Y human neuroblastoma cell line","author":"Shipley","year":"2016","journal-title":"J. Vis. Exp."},{"key":"B35","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B36","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.stem.2014.06.008","article-title":"Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow","volume":"15","author":"Zhou","year":"2014","journal-title":"Cell Stem Cell"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2023.1286280\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T04:10:10Z","timestamp":1698379810000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2023.1286280\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,25]]},"references-count":36,"alternative-id":["10.3389\/fcell.2023.1286280"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2023.1286280","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,25]]},"article-number":"1286280"}}