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• W4383534859 abstract "Intervertebral disc degeneration (IVDD) is closely associated with the structural damage in the annulus fibrosus (AF). Aberrant mechanical loading is an important inducement of annulus fibrosus cells (AFCs) apoptosis, which contributes to the AF structural damage and aggravates IVDD, but the underlying mechanism is still unclear. This study aims to investigate the mechanism of a mechanosensitive ion channel protein Piezo1 in aberrant mechanical loading-induced AFCs apoptosis and IVDD.Rats were subjected to lumbar instability surgery to induce the unbalanced dynamic and static forces to establish the lumbar instability model. MRI and histological staining were used to evaluate the IVDD degree. A cyclic mechanical stretch (CMS)-stimulated AFCs apoptosis model was established by a Flexcell system in vitro. Tunel staining, mitochondrial membrane potential (MMP) detection, and flow cytometry were used to evaluate the apoptosis level. The activation of Piezo1 was detected using western blot and calcium fluorescent probes. Chemical activator Yoda1, chemical inhibitor GSMTx4, and a lentiviral shRNA-Piezo1 system (Lv-Piezo1) were utilized to regulate the function of Piezo1. High-throughput RNA sequencing (RNA-seq) was used to explore the mechanism of Piezo1-induced AFCs apoptosis. The Calpain activity and the activation of Calpain2/Bax/Caspase3 axis were evaluated by the Calpain activity kit and western blot with the siRNA-mediated Calapin1 or Calpain2 knockdown. Intradiscal administration of Lv-Piezo1 was utilized to evaluate the therapeutic effect of Piezo1 silencing in IVDD rats.Lumbar instability surgery promoted the expression of Piezo1 in AFCs and stimulated IVDD in rats 4 weeks after surgery. CMS elicited distinct apoptosis of AFCs, with enhanced Piezo1 activation. Yoda1 further promoted CMS-induced apoptosis of AFCs, while GSMTx4 and Lv-Piezo1 exhibited opposite effects. RNA-seq showed that knocking down Piezo1 inhibited the calcium signaling pathway. CMS enhanced Calpain activity and elevated the expression of BAX and cleaved-Caspase3. Calpain2, but not Calpain1 knockdown, inhibited the expression of BAX and cleaved-Caspase3 and alleviated AFCs apoptosis. Lv-Piezo1 significantly alleviated the progress of IVDD in rats after lumbar instability surgery.Aberrant mechanical loading induces AFCs apoptosis to promote IVDD by activating Piezo1 and downstream Calpain2/BAX/Caspase3 pathway. Piezo1 is expected to be a potential therapeutic target in treating IVDD." @default.
• W4383534859 created "2023-07-08" @default.
• W4383534859 creator A5006091982 @default.
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• W4383534859 date "2023-07-07" @default.
• W4383534859 modified "2023-10-16" @default.
• W4383534859 title "Aberrant mechanical loading induces annulus fibrosus cells apoptosis in intervertebral disc degeneration via mechanosensitive ion channel Piezo1" @default.
• W4383534859 cites W1745281255 @default.
• W4383534859 cites W1923210590 @default.
• W4383534859 cites W1966176339 @default.
• W4383534859 cites W1991091521 @default.
• W4383534859 cites W1999720993 @default.
• W4383534859 cites W2000723582 @default.
• W4383534859 cites W2005298420 @default.
• W4383534859 cites W2009033768 @default.
• W4383534859 cites W2016540525 @default.
• W4383534859 cites W2019246150 @default.
• W4383534859 cites W2020418292 @default.
• W4383534859 cites W2024221619 @default.
• W4383534859 cites W2026038471 @default.
• W4383534859 cites W2029931091 @default.
• W4383534859 cites W2030871870 @default.
• W4383534859 cites W2031545788 @default.
• W4383534859 cites W2039649884 @default.
• W4383534859 cites W2040939772 @default.
• W4383534859 cites W2046329142 @default.
• W4383534859 cites W2047129015 @default.
• W4383534859 cites W2047613950 @default.
• W4383534859 cites W2051624587 @default.
• W4383534859 cites W2059100011 @default.
• W4383534859 cites W2067219797 @default.
• W4383534859 cites W2071453006 @default.
• W4383534859 cites W2078579431 @default.
• W4383534859 cites W2087959061 @default.
• W4383534859 cites W2088250645 @default.
• W4383534859 cites W2088329049 @default.
• W4383534859 cites W2099323502 @default.
• W4383534859 cites W2100441031 @default.
• W4383534859 cites W2107634021 @default.
• W4383534859 cites W2108652316 @default.
• W4383534859 cites W2112464066 @default.
• W4383534859 cites W2136533772 @default.
• W4383534859 cites W2146961217 @default.
• W4383534859 cites W2151388489 @default.
• W4383534859 cites W2151819466 @default.
• W4383534859 cites W2168547803 @default.
• W4383534859 cites W2266738216 @default.
• W4383534859 cites W2339490761 @default.
• W4383534859 cites W2527503499 @default.
• W4383534859 cites W2530833951 @default.
• W4383534859 cites W2577243894 @default.
• W4383534859 cites W2734378294 @default.
• W4383534859 cites W2738059027 @default.
• W4383534859 cites W2785150634 @default.
• W4383534859 cites W2845489947 @default.
• W4383534859 cites W2898529442 @default.
• W4383534859 cites W2901270382 @default.
• W4383534859 cites W2903271691 @default.
• W4383534859 cites W2914765011 @default.
• W4383534859 cites W2916651092 @default.
• W4383534859 cites W2951494953 @default.
• W4383534859 cites W2969725318 @default.
• W4383534859 cites W2979864881 @default.
• W4383534859 cites W2981365899 @default.
• W4383534859 cites W2982149393 @default.
• W4383534859 cites W2988803734 @default.
• W4383534859 cites W3033303495 @default.
• W4383534859 cites W3122897669 @default.
• W4383534859 cites W3125259346 @default.
• W4383534859 cites W3128846620 @default.
• W4383534859 cites W3135159127 @default.
• W4383534859 cites W3136477065 @default.
• W4383534859 cites W3137979698 @default.
• W4383534859 cites W3160383251 @default.
• W4383534859 cites W3170429079 @default.
• W4383534859 cites W3173616315 @default.
• W4383534859 cites W3188300656 @default.
• W4383534859 cites W3189609051 @default.
• W4383534859 cites W3203743280 @default.
• W4383534859 cites W3205847864 @default.
• W4383534859 cites W4213417750 @default.
• W4383534859 cites W4214595327 @default.
• W4383534859 cites W4220674201 @default.
• W4383534859 cites W4225793598 @default.
• W4383534859 cites W4280533055 @default.
• W4383534859 cites W4281296177 @default.
• W4383534859 cites W4281571325 @default.
• W4383534859 cites W4285040792 @default.
• W4383534859 cites W4285732333 @default.
• W4383534859 cites W4290839787 @default.

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