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Unexpectedly, no previous studies have demonstrated the association and the underlying mechanism between nucleus pulposus tissue degeneration and calcification formation. Secreted Phosphoprotein 1 (SPP1) exerts crucial functions in bone matrix mineralization and calcium deposition. Here, a novel function of SPP1 is reported, namely that it can aggravate nucleus pulposus cells (NPs) degeneration by negatively regulating extracellular matrix homeostasis. The degenerated NPs have a higher mineralization potential, which is achieved by SPP1. Mechanistically, SPP1 can accelerate the degeneration of nucleus pulposus cells by activating integrin \u03b15\u03b21 (ITG\u03b15\/\u03b21), aggravating mitochondrial damage and inhibiting mitophagy. SPP1\u2010ITG\u03b15\/\u03b21 axis inhibits mitophagy by PINK1\/PARKIN pathway blockade. In conclusion, SPP1 activates ITG\u03b15\/\u03b21 to inhibit mitophagy, accelerates NPs degeneration, and induces calcification, thereby leading to intervertebral disc degeneration (IVDD) and calcification, identifying the potentially unknown mechanism and relationship between IVDD and calcification. Important insights are provided into the role of SPP1 in nucleus pulposus calcification in IVDD by inducing nucleus pulposus cell senescence through inhibition of mitophagy and may help develop potential new strategies for IVDD treatment.<\/jats:p>","DOI":"10.1002\/advs.202411162","type":"journal-article","created":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T12:33:37Z","timestamp":1735130017000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["SPP1\u2010ITG\u03b15\/\u03b21 Accelerates Calcification of Nucleus Pulposus Cells by Inhibiting Mitophagy via Ubiquitin\u2010Dependent PINK1\/PARKIN Pathway Blockade"],"prefix":"10.1002","volume":"12","author":[{"given":"Hanwen","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Orthopedic Qilu Hospital of Shandong University Jinan Shandong 250012 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