Moelle épinière - Publications Scientifiques

Dernière publication 01/03/2026

CRISPLD2 Attenuates Intervertebral Disc Degeneration by Suppressing Oxidative St

To investigate whetherCrispld2deficiency in intervertebral discs contributes to the progression of IVDD, NP-specificCrispld2-cKO mice were...

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    [title] => CRISPLD2 Attenuates Intervertebral Disc Degeneration by Suppressing Oxidative St
    [paragraph] => CRISPLD2 Attenuates Intervertebral Disc Degeneration by Suppressing Oxidative Stress-Induced Ferroptosis through the miR-548I-IL17A Axis
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Authors
Yangyang Shi, Fudong Li, Tianyi Zhao, Kaiqiang Sun, Danying Zhang, Chen Yan, Ximing Xu, Jingchuang Sun, Xulin Hu, Xin Yong, Jiangang Shi, Yuan Wang

Lab
Journal
Advanced Science
Abstract
To investigate whetherCrispld2deficiency in intervertebral discs contributes to the progression of IVDD, NP-specificCrispld2-cKO mice were established. Both lumbar and coccygeal discs were examined in parallel to ensure consistent observations across spinal levels. Histological analysis of both lumbar and caudal intervertebral discs using H&E and SOFG staining revealed pronounced matrix disorganization and proteoglycan loss in theCrispld2-cKO group, with significantly higher histological scores compared toCrispld2fl/flcontrols (Figure2A,F). IF staining further showed thatCrispld2deficiency led to a marked reduction of Acan and a concomitant increase in Mmp3 expression in the NP region of both lumbar and coccygeal discs (Figure2B,G). Consistent with the histological changes, MRI imaging demonstrated reduced signal intensity in both discs ofCrispld2-cKO mice, reflecting disc dehydration and structural compromise afterCrispld2deletion (Figure2C,H). The Pfirrmann grading score further confirmed the above result (Figure2C,H). The WB results of NP tissues from lumbar and coccygeal discs revealed markedly reduced levels of Crispld2, Acan, and Col2a1, along with elevated expression of Mmp3 and Adamts5 inCrispld2-cKO mice, confirming molecular features of matrix degradation (Figure2D,I). Quantitative analysis of the protein levels was presented in FigureS7. The co-immunofluorescence of Acan and Mmp3 for the primary NPCs from theCrispld2fl/flandCrispld2-cKO mice further confirmed the above findings (Figure2E,J). Additionally, behavioral assessments of theCrispld2fl/flandCrispld2-cKO mice at 2, 10, and 18 months revealed a significant decline in functional mobility (both distance travel and max speed), pressure tolerance, and active time in theCrispld2-cKO group, indicatingCrispld2deficiency-induced disc degeneration might result in hyperalgesia (Figure2K). Collectively, these results demonstrated that Crispld2 is essential for maintaining intervertebral disc structural integrity and ECM homeostasis, and that its deficiency leads to progressive disc degeneration and associated pain-like behaviors.
Keywords/Topics
CRISPLD2; ferroptosis; intervertebral disc degeneration; nucleus pulposus cells; miRNA
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