{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T22:49:09Z","timestamp":1786574949119,"version":"build-2736575974"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:00:00Z","timestamp":1701129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthopaedic Surgery"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Mechanisms involved in developing intervertebral disc degeneration (IDD) are poorly understood, thus making developing effective therapies difficult. This study aimed to suggest a possible molecular mechanism, based on transcriptome sequencing\u2010identified transforming growth factor (TGF\u2010\u03b2), underlying the effects on bone homeostasis in IDD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A mouse model for IDD was established. Transcriptome sequencing of nucleus pulposus tissue from mice (<jats:italic>n<\/jats:italic>\u2009=\u20093) identified differentially expressed mRNAs and key genes impacting bone homeostasis. A protein\u2013protein interaction network pinpointed core genes. GO and KEGG analysis revealed gene functions. Expression levels of TGF\u2010\u03b21, tartrate\u2010resistant acid phosphatase (TRAP), and cathepsin K\u2009(CTSK) were measured. Micro\u2010CT evaluated vertebral structures and vascular imaging. Western Blot measured expression levels of Vegf, Opn, MMP3, and MMP13. Safranin O\u2010Fast Green and TRAP staining were performed on intervertebral discs and endplates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Transcriptomic analysis found 1790 differentially expressed mRNAs in IDD mice. Twenty\u2010eight genes related to bone homeostasis in IDD were identified. TGF\u2010\u03b21 was confirmed as the core gene. GO and KEGG showed TGF\u2010\u03b21 regulates osteoclast markers like CTSK and TRAP through pathways including NF\u2010\u03baB and MAPK. Experimental validation revealed lower TGF\u2010\u03b21 expression in IDD mice than controls, and increased TRAP and CTSK expression. Micro\u2010CT showed decreased bone mass and intervertebral disc space in IDD mice. Vascular imaging showed increased vascular volume in IDD cartilaginous endplates. Western blot displayed increased VEGF and OPN levels, but decreased MMP3 and MMP13 in IDD mice. Safranin O\u2010fast green staining revealed severe IDD degeneration. However, TGF\u2010\u03b21 injection improved bone parameters in IDD mice. <jats:italic>In vitro<\/jats:italic> experiments confirmed TGF\u2010\u03b21 inhibits bone marrow macrophages differentiation into osteoclasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>From our data, we conclude that TGF\u2010\u03b21 repressed osteoclast differentiation and aberrant bone\u2010associated angiogenesis in cartilage endplates (EPs) to alleviate IDD, which may be instrumental for the therapeutic targeting of IDD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/os.13912","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T08:57:02Z","timestamp":1701161822000},"page":"167-182","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["TGF\u2010\u03b21 Inhibits Osteoclast Differentiation and Abnormal Angiogenesis in Intervertebral Disc Degeneration: Evidence from RNA Sequencing and Animal Studies"],"prefix":"10.1111","volume":"16","author":[{"given":"Keping","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopedics Second Hospital of Lanzhou University  Lanzhou China"},{"name":"Key Laboratory of Orthopedics Disease of Gansu Province  Lanzhou China"},{"name":"Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuolong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Second Hospital of Lanzhou University  Lanzhou China"},{"name":"Key Laboratory of Orthopedics Disease of Gansu Province  Lanzhou China"},{"name":"Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyang","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Second Hospital of Lanzhou University  Lanzhou China"},{"name":"Key Laboratory of Orthopedics Disease of Gansu Province  Lanzhou 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