PINK1/Parkin介导的线粒体自噬在力学失衡诱导终板软骨退变中的作用

郑权; 吴明凡; 邵松; 孙良业; 许俊胜

doi:10.11659/jjssx.03E023153

您当前的位置：

首页 >

文章列表页 >

PINK1/Parkin介导的线粒体自噬在力学失衡诱导终板软骨退变中的作用

基础研究 | 更新时间：2024-04-01

- PINK1/Parkin介导的线粒体自噬在力学失衡诱导终板软骨退变中的作用
- The role of PINK1/Parkin-mediated mitophagy in mechanical imbalance-induced endplate cartilage degeneration
- 局解手术学杂志 2024年33卷第3期页码：189-193
- 作者机构：
  
  安徽医科大学附属六安医院骨科，安徽六安 237001
- 作者简介：
  
  许俊胜，E-mail：zhy202307@163.com
- 基金信息：
  
  国家自然科学基金(82102629);安徽省重点研究与开发计划人口健康专项(202004j07020003);安徽医科大学校科研基金(2021xkj097)
- DOI：10.11659/jjssx.03E023153
  中图分类号： R-332;R681.5
- 纸质出版日期：2024-03-25，
  
  收稿日期：2023-03-24，
扫描看全文
郑权,吴明凡,邵松等.PINK1/Parkin介导的线粒体自噬在力学失衡诱导终板软骨退变中的作用[J].局解手术学杂志,2024,33(03):189-193.

ZHENG Quan,WU Ming-fan,SHAO Song,et al.The role of PINK1/Parkin-mediated mitophagy in mechanical imbalance-induced endplate cartilage degeneration[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(03):189-193.
郑权,吴明凡,邵松等.PINK1/Parkin介导的线粒体自噬在力学失衡诱导终板软骨退变中的作用[J].局解手术学杂志,2024,33(03):189-193. DOI： 10.11659/jjssx.03E023153.

ZHENG Quan,WU Ming-fan,SHAO Song,et al.The role of PINK1/Parkin-mediated mitophagy in mechanical imbalance-induced endplate cartilage degeneration[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(03):189-193. DOI： 10.11659/jjssx.03E023153.

摘要

目的

检测脊柱失稳诱导终板软骨退变模型大鼠中线粒体自噬水平的变化，探讨PINK1/Parkin介导的线粒体自噬在终板软骨以及椎间盘退变中的作用。

方法

通过手术切除大鼠L

棘上、棘间韧带，咬除L

两侧关节突，构建大鼠脊柱失稳模型。18只SD大鼠分为正常组、退变组及羰基氰化物3-氯苯腙（CCCP）组，每组6只。正常组大鼠无特殊处理，退变组大鼠构建大鼠脊柱失稳模型，CCCP组大鼠在构建大鼠脊柱失稳模型后于椎间盘注射5 μL CCCP （10 μmol/L ）。利用HE染色观察终板软骨及椎间盘形态变化，番红-固绿染色观察终板软骨细胞外基质变化。 RT-PCR检测各组大鼠终板软骨组织中Ⅱ型胶原（COL-2A）、蛋白聚糖（ACAN）、PINK1、Parkin mRNA表达水平；Western blot检测COL-2A、ACAN、PINK1、Parkin及线粒体膜蛋白Tomm20、Timm23蛋白表达水平变化。

结果

与正常组比较，退变组大鼠椎间盘髓核破坏明显，终板软骨细胞外基质分泌减少；CCCP组大鼠椎间盘结构较完整，终板软骨细胞外基质分泌较退变组明显增多。与正常组比较，退变组大鼠终板软骨组织COL-2A、ACAN表达均明显下调（

0.05），线粒体自噬相关基因PINK1和Parkin表达显著降低（

0.05），线粒体膜蛋白Tomm20及Timm23表达增高（

0.05）；CCCP组大鼠终板软骨组织COL-2A、ACAN、PINKI及Parkin表达较退变组均明显上调（

0.05），Tomm20及Timm23蛋白水平较退变组明显下调（

0.05）。

结论

大鼠脊柱失稳导致终板软骨PINK1/Parkin信号通路介导的线粒体自噬水平降低，从而诱导终板软骨及椎间盘退变，激活线粒体自噬能够明显减轻终板软骨及椎间盘退变。

Abstract

Objective

To detect the changes of mitophagy level in rats with endplate cartilage degeneration induced by spinal instability，and explore the role of PINK1/Parkin-mediated mitophagy in endplate cartilage and intervertebral disc degeneration.

Methods

The rat spinal instability model was established by surgically removing the superspinal and interspinal ligaments of L

to L

，and cleaning the bilateral articular processes of the L

to L

.Eighteen SD rats were divided into the normal group，the degenerative group，and the carbonyl cyanide 3-chlorophenylhydrazone （CCCP） group，with 6 rats in each group.The rats in the normal group had no special treatment，the rats in the degenerative group constructed a rat spinal instability model，and the rats in the CCCP group were injected with 5 μL of CCCP （10 μmol/L） in the intervertebral disc after the construction of spinal instability model.The changes of histomorphology in the endplate cartilage and intervertebral disc were abserved by HE staining，and the change of extracellular matrix of endplate cartilage was observed by safranin O-fast green staining.RT-PCR detected the mRNA expression of type Ⅱ collagen （COL-2A），aggrecan （ACAN），PINK1 and Parkin in each group.The changes of the protein expression levels of COL-2A，ACAN，PINK1，Parkin and mitochondrial membrane proteins of Tomm20 and Timm23 were detected by Western blot.

Results

Compared with the normal group，the intervertebral disc nucleus pulposus of rats in the degenerative group was significantly destroyed and the secretion of extracellular matrix of endplate chondrocytes decreased；while the structure of intervertebral discs for rats in the CCCP group was more intact，and the secretion of extracellular matrix of endplate chondrocytes was significantly increased compared with that in the degenerative group.Compared with the normal group，the expression of COL-2A and ACAN in endplate cartilage tissues of rats in the degenerative group were significantly down-regulated （

0.05），the expression of mitochondrial autophagy-related genes of PINK1 and Parkin were significantly decreased （

0.05），and the expression of mitochondrial membrane proteins of Tomm20 and Timm23 were increased （

0.05）.Compared with the degenerative group，the expression of COL-2A，ACAN，PINKI and Parkin in the endplate cartilage tissue of rats in the CCCP group were significantly up-regulated （

0.05），and the protein levels of Tomm20 and Timm23 were significantly down-regulated （

0.05）.

Conclusion

Rat spinal instability leads to a decrease level of mitophagy mediated by PINK1/Parkin signaling pathway in endplate cartilage，thereby inducing endplate cartilage and intervertebral disc degeneration，and the activation of mitophagy can significantly reduce endplate cartilage and intervertebral disc degeneration.

关键词

脊柱失稳终板软骨椎间盘退变线粒体自噬PINK1/Parkin信号通路

Keywords

spinal instabilityendplate cartilageintervertebral disc degenerationmitophagyPINK1/Parkin signaling pathway

references

Grunhagen T，Shirazi-Adl A，Fairbank JCT，et al.Intervertebral disk nutrition： a review of factors influencing concentrations of nutrients and metabolites［J］.Orthop Clin North Am，2011，42（4）：465-477.doi：10.1016/j.ocl.2011.07.010http://dx.doi.org/10.1016/j.ocl.2011.07.010.

Zehra U，Bow C，Lotz JC，et al.Structural vertebral endplate nomenclature and etiology： a study by the ISSLS spinal phenotype focus group［J］.Eur Spine J，2018，27（1）：2-12.doi：10.1007/s00586-017-5292-3http://dx.doi.org/10.1007/s00586-017-5292-3.

Navone SE，Peroglio M，Guarnaccia L，et al.Mechanical loading of intervertebral disc modulates microglia proliferation，activation，and chemotaxis［J］.Osteoarthritis Cartilage，2018，26（7）：978-987.doi： 10.1016/j.joca.2018.04.013http://dx.doi.org/10.1016/j.joca.2018.04.013.

王书君，谭慧琼，袁杰.热休克蛋白A12B介导COX-2表达调控心肌缺血再灌注损伤中心肌细胞线粒体自噬的作用研究［J］.局解手术学杂志，2022，31（9）：759-765.doi：10.11659/jjssx.04E022035http://dx.doi.org/10.11659/jjssx.04E022035.

王培，付宇.线粒体自噬与疾病［J］.河北医科大学学报，2018，39（7）：853-857.doi：10.3969/j.issn.1007-3205.2018.07.027http://dx.doi.org/10.3969/j.issn.1007-3205.2018.07.027.

Jin Z，Chang B，Wei Y，et al.Curcumin exerts chondroprotective effects against osteoarthritis by promoting AMPK/PINK1/Parkin-mediated mitophagy［J］.Biomed Pharmacother，2022，151：113092.doi：10.1016/j.biopha.2022.113092http://dx.doi.org/10.1016/j.biopha.2022.113092.

Kim H，Hong JY，Lee J，et al.IL-1β promotes disc degeneration and inflammation through direct injection of intervertebral disc in a rat lumbar disc herniation model［J］.Spine J，2021，21（6）：1031-1041.doi：10.1016/j.spinee.2021.01.014http://dx.doi.org/10.1016/j.spinee.2021.01.014.

Wong J,Sampson SL,Bell-Briones H,et al.Nutrient supply and nucleus pulposus cell function: effects of the transport properties of the cartilage endplate and potential implications for intradiscal biologic therapy[J]. Osteoarthritis Cartilage,2019,27（6）:956-964. doi: 10.1016/j.joca.2019.01.013http://dx.doi.org/10.1016/j.joca.2019.01.013.

Neidlinger-Wilke C，Boldt A，Brochhausen C，et al.Molecular interactions between human cartilaginous endplates and nucleus pulposus cells［J］.Spine （Phila Pa 1976），2014，39（17）：1355-1364.doi：10.1097/BRS.0000000000000372http://dx.doi.org/10.1097/BRS.0000000000000372.

董福慧.脊柱失稳的因素及其对策［J］.中国骨伤，2008，21（8）：563-565.doi：10.3969/j.issn.1003-0034.2008.08.001http://dx.doi.org/10.3969/j.issn.1003-0034.2008.08.001.

Chang SH，Mori D，Kobayashi H，et al.Excessive mechanical loading promotes osteoarthritis through the gremlin-1-NF-κB pathway［J］.Nat Commun，2019，10（1）：1442.doi：10.1038/s41467-019-09491-5http://dx.doi.org/10.1038/s41467-019-09491-5.

Ansari MY，Khan NM，Ahmad I，et al.Parkin clearance of dysfunctional mitochondria regulates ROS levels and increases survival of human chondrocytes［J］.Osteoarthritis Cartilage，2018，26（8）：1087-1097.doi：10.1016/j.joca.2017.07.020http://dx.doi.org/10.1016/j.joca.2017.07.020.

Wang C，Yang Y，Zhang Y，et al.Protective effects of metformin against osteoarthritis through upregulation of SIRT3-mediated PINK1/Parkin-dependent mitophagy in primary chondrocytes［J］.Biosci Trends，2019，12（6）：605-612.doi：10.5582/bst.2018.01263http://dx.doi.org/10.5582/bst.2018.01263.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

长链非编码RNA调控椎间盘退变的研究进展

椎间盘源性腰痛的诊断及治疗进展

薯蓣皂苷通过调节人髓核细胞TLR4/NF-κB信号通路抑制IL-1β诱导的分解代谢和凋亡