SPP1-ITGα5/β1 Accelerates Calcification of Nucleus Pulposus Cells by Inhibiting Mitophagy via Ubiquitin-Dependent PINK1/PARKIN Pathway Blockade

被引：1

作者：

Gu, Hanwen ^{[1
]}

Li, Qi ^{[1
]}

Liu, Zhenchuan ^{[1
]}

Li, Yanlin ^{[1
]}

Liu, Kaiwen ^{[1
]}

Kong, Xiangzhen ^{[1
]}

Zhang, Yuanqiang ^{[1
]}

Meng, Qunbo ^{[1
]}

Song, Kangle ^{[1
]}

Xie, Qing ^{[2
]}

Gao, Yuan ^{[1
]}

Cheng, Lei ^{[1
]}

机构：

[1] Shandong Univ, Qilu Hosp, Dept Orthoped, Jinan 250012, Shandong, Peoples R China

[2] Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Dept Pharm, Jinan 250012, Peoples R China

来源：

ADVANCED SCIENCE | 2025年 / 12卷 / 07期

基金：

中国国家自然科学基金;

关键词：

calcification; integrin alpha 5 beta 1; intervertebral disc degeneration; mitophagy; nucleus pulposus cells; secreted phosphoprotein 1; MECHANISMS; SENESCENCE; DISCS;

D O I：

10.1002/advs.202411162

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Low back pain (LBP) caused by nucleus pulposus degeneration and calcification leads to great economic and social burden worldwide. 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 alpha 5 beta 1 (ITG alpha 5/beta 1), aggravating mitochondrial damage and inhibiting mitophagy. SPP1-ITG alpha 5/beta 1 axis inhibits mitophagy by PINK1/PARKIN pathway blockade. In conclusion, SPP1 activates ITG alpha 5/beta 1 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.

引用

页数：16

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