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Mechanical stimulation (MS) plays an important role in OPLL. DLX5 is an essential transcription factor required for osteoblast differentiation. However, the role of DLX5 during in OPLL is unclear. This study aims to investigate whether DLX5 is associated with OPLL progression under MS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Stretch stimulation was applied to spinal ligaments cells derived from OPLL (OPLL cells) and non\u2010OPLL (non\u2010OPLL cells) patients. Expression of DLX5 and osteogenesis\u2010related genes were determined by quantitative real\u2010time polymerase chain reaction and Western blot. The osteogenic differentiation ability of the cells was measured using alkaline phosphatase (ALP) staining and alizarin red staining. The protein expression of DLX5 in the tissues and the nuclear translocation of NOTCH intracellular domain (NICD) was examined by immunofluorescence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with non\u2010OPLL cells, OPLL cells expressed higher levels of DLX5 in vitro and vivo (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). Upregulated expression of DLX5 and osteogenesis\u2010related genes (OSX, RUNX2, and OCN) were observed in OPLL cells induced with stretch stimulation and osteogenic medium, whereas there was no change in the non\u2010OPLL cells (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). Cytoplasmic NICD protein translocated from the cytoplasm to the nucleus inducing DLX5 under stretch stimulation, which was reduced by the NOTCH signaling inhibitors (DAPT) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data suggest that DLX5 play a critical role in MS\u2010induced progression of OPLL through NOTCH signaling, which provides a new insight into the pathogenesis of OPLL.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsp2.1247","type":"journal-article","created":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T12:04:47Z","timestamp":1674907487000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["<scp>DLX5<\/scp> regulates the osteogenic differentiation of spinal ligaments cells derived from ossification of the posterior longitudinal ligament patients via <scp>NOTCH<\/scp> signaling"],"prefix":"10.1002","volume":"6","author":[{"given":"Tao","family":"Tang","sequence":"first","affiliation":[{"name":"Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital Sun Yat\u2010sen University  Shenzhen China"},{"name":"Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Orthopaedic Research Institute\/Department of Spinal Surgery The First Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengya","family":"Zhu","sequence":"additional","affiliation":[{"name":"Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital Sun Yat\u2010sen University  Shenzhen 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