{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:21:55Z","timestamp":1785424915375,"version":"3.56.0"},"reference-count":43,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NIH-1R01AR076427-01"],"award-info":[{"award-number":["NIH-1R01AR076427-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"award":["NIH-1R01AR076427-01"],"award-info":[{"award-number":["NIH-1R01AR076427-01"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Department of Orthopaedics at Emory University School of Medicine"},{"id":[{"id":"https:\/\/ror.org\/03czfpz43","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Low back pain is closely associated with intervertebral disc (IVD) degeneration, in which inflammation and neovascularization within the annulus fibrosus (AF) contribute to pain generation. Platelet-derived growth factor (PDGF)-BB plays a crucial role in tissue repair and cellular homeostasis, but its role in AF cell biology remains poorly understood. To investigate the effects of PDGF-BB on human AF cells, healthy and degenerated AF cells were treated with PDGF-BB for 3 or 5 days, followed by bulk RNA sequencing. Functional enrichment of differentially expressed genes, transcription factor activity analysis, and protein\u2013protein interaction network analysis was performed. Publicly available single-cell RNA-seq data were used to compare the transcriptomic profiles of native healthy and degenerated AF samples. In addition, TNF-\u03b1 stimulation was conducted to validate the anti-inflammatory effects of PDGF-BB. Our findings suggest that PDGF-BB induced both common and context-dependent transcriptional responses in healthy and degenerated AF cells. In healthy AF cells, PDGF-BB consistently upregulated genes associated with cell cycle and developmental growth. In degenerated AF cells, PDGF-BB also induced these responses, while additionally it downregulated the genes related to extracellular matrix remodeling and collagen degradation. Meanwhile, PDGF-BB showed common effects in both healthy and degenerated cells by modulating the expression of genes within G protein-coupled receptor (GPCR) networks that are linked to complement, inflammation, and neurotransmitter signaling. In addition, PDGF-BB also suppressed the expression of genes involved in inflammatory-neurogenic signaling, including nerve growth factor (NGF), C-X-C motif chemokine ligand 12 (CXCL12), and apolipoprotein E (APOE). To relate these PDGF-BB induced responses to disc degeneration, we reanalyzed publicly available single-cell RNA-seq datasets from native human AF tissues and found that NGF-positive cells showed increased tumor necrosis factor (TNF)-\u03b1 signaling activity. When AF cells were stimulated with TNF-\u03b1, PDGF-BB treatment significantly inhibited the expression of NGF, endothelin-1 (EDN1), and interleukin 6 (IL6) under both baseline and TNF-\u03b1-stimulated conditions. These results suggest that PDGF-BB modulates gene expression associated with inflammatory and neurogenic signaling as well as ECM remodeling in human AF cells, providing a transcriptomic insight into the PDGF-BB\u2019s function in AF biology.<\/jats:p>","DOI":"10.3390\/cells15111007","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T08:09:16Z","timestamp":1780301356000},"page":"1007","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic Signature of PDGF-BB Control of Annulus Fibrosus Reveals Modulation of Inflammatory and Neurogenic Pathways"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1170-0374","authenticated-orcid":false,"given":"Changli","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, School of Medicine, Emory University, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, School of Medicine, Emory University, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua W.","family":"McNulty","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, School of Medicine, Emory University, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1897-3008","authenticated-orcid":false,"given":"David","family":"Berenfeld","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, School of Medicine, Emory University, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1288-2149","authenticated-orcid":false,"given":"Lisbet","family":"Haglund","sequence":"additional","affiliation":[{"name":"Department of Surgery, McGill University, Montreal, QC H4A3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1010-6952","authenticated-orcid":false,"given":"Sangwook Tim","family":"Yoon","sequence":"additional","affiliation":[{"name":"Emory Orthopaedics & Spine Center, Atlanta, GA 30329, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Goh","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, School of Medicine, Emory University, Atlanta, GA 30329, USA"},{"name":"Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hicham","family":"Drissi","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, School of Medicine, Emory University, Atlanta, GA 30329, USA"},{"name":"Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1007\/s00586-017-5432-9","article-title":"The Global Spine Care Initiative: A summary of the global burden of low back and neck pain studies","volume":"27","author":"Hurwitz","year":"2018","journal-title":"Eur. 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