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In the vertebral growth plate, adjacent to the disc, powerful growth plate morphogens (GPMs) modulate this growth. We evaluated whether GPMs can also alter the capacity of annulus fibrosus (AF) disc cells to proliferate and\/or remodel their extracellular matrix (ECM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>AF cell responsiveness to seven GPMs was screened in monolayer culture by RT\u2010qPCR for downstream signaling markers. GPMs and concentrations eliciting significant transcriptional responses were selected for deeper analysis. Bulk RNA sequencing (RNA\u2010seq) was conducted on AF cells cultured in a 2.5D environment to preserve their native elongated phenotype. Differentially expressed genes (DEGs) were identified and subjected to Gene Ontology enrichment, focusing on ECM remodeling and cell\u2010proliferation processes. Transcriptomic findings were corroborated by assessments of cell proliferation (DNA content), sulfated glycosaminoglycan (sGAG) levels, and matrix metalloproteinase (MMP) activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>BMP\u20102, TGF\u2010\u03b21, and FGF\u20102 significantly altered AF cell expression of downstream target genes, whereas Ihh, PTHrP, Wnt\u20101, and FGF\u201018 did not. IGF\u20101 induced modest, dose\u2010dependent gene expression changes that were not replicated by RNA\u2010seq. BMP\u20102 and TGF\u2010\u03b21 upregulated genes associated with anabolic ECM remodeling. BMP\u20102 promoted a cartilage\u2010like ECM with increased expression of type II\u2010associated collagens, aggrecan, and hyaluronan synthesis. TGF\u2010\u03b21 promoted type I collagen\u2010associated genes, collagen cross\u2010linking, and myofibroblast activation. In contrast, FGF\u20102 activated transcriptional programs related to cell\u2010cycle progression, collagen degradation, and increased GAG turnover. Functionally, we observed higher DNA content under BMP\u20102 and TGF\u2010\u03b21 stimulation and higher sGAG levels under BMP\u20102, TGF\u2010\u03b21, and FGF\u20102 treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BMP\u20102, TGF\u2010\u03b21, and FGF\u20102 can modulate AF cell behavior, influencing tissue remodeling and implicating their involvement in disc wedging during AIS onset.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsp2.70212","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T08:02:10Z","timestamp":1787385730000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Growth Plate Morphogens as Potential Modulators of Cellular Tissue Remodeling by Annulus Fibrosus Cells"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9819-6421","authenticated-orcid":false,"given":"K.","family":"Stradovnik\u2010Poikilidis","sequence":"first","affiliation":[{"name":"Orthopaedic Biomechanics, Department of Biomedical Engineering Eindhoven University of Technology  Eindhoven the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0119-3257","authenticated-orcid":false,"given":"M.","family":"Teunissen","sequence":"additional","affiliation":[{"name":"Department Clinical Sciences, Faculty of Veterinary Medicine Utrecht University  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4732-9447","authenticated-orcid":false,"given":"F. 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