Inhibition of lysyl oxidase accelerates intervertebral disc degeneration induced by apoptosis of nucleus pulposus cells

Jianmin LI; Hui XING; Fanli CHONG; Runzhi ZHAO; Bo HUANG

doi:10.16016/j.2097-0927.202305043

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Inhibition of lysyl oxidase accelerates intervertebral disc degeneration induced by apoptosis of nucleus pulposus cells

Basic Medicine | 更新时间：2026-01-09

- Inhibition of lysyl oxidase accelerates intervertebral disc degeneration induced by apoptosis of nucleus pulposus cells
- Journal of Army Medical University Vol. 45, Issue 19, Pages: 2029-2036(2023)
- 作者机构：
  
  400037 重庆，陆军军医大学(第三军医大学)第二附属医院骨科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81972114);the Basic Research and Frontier Exploration Program of Chongqing(cstc2019jcyj-msxmX0022)
- DOI：10.16016/j.2097-0927.202305043
  CLC： R345;R363.21;R681.53
- Received：15 May 2023，
  
  Revised：2023-07-12，
  
  Published：15 October 2023
- 稿件说明：
移动端阅览
Jianmin LI, Hui XING, Fanli CHONG, et al. Inhibition of lysyl oxidase accelerates intervertebral disc degeneration induced by apoptosis of nucleus pulposus cells[J]. Journal of Army Medical University, 2023, 45(19): 2029-2036.
DOI：

Jianmin LI, Hui XING, Fanli CHONG, et al. Inhibition of lysyl oxidase accelerates intervertebral disc degeneration induced by apoptosis of nucleus pulposus cells[J]. Journal of Army Medical University, 2023, 45(19): 2029-2036. DOI： 10.16016/j.2097-0927.202305043.

摘要

目的

探讨赖氨酰氧化酶(lysyl oxidase

LOX)在椎间盘年龄相关性退变中发挥的作用及可能机制。

方法

选取2、8和20月龄的SD大鼠各3只，拍摄椎间盘核磁共振与X线，评估年龄对椎间盘退变的影响；分离不同年龄椎间盘组织蛋白，利用Western blot检测LOX蛋白的表达量；利用CoCl

建立髓核细胞缺氧凋亡模型；LOX蛋白抑制剂BAPN及pcDNA3.1(+)-LOX重组质粒处理髓核细胞，研究LOX蛋白对不同缺氧环境下髓核细胞凋亡的作用；15只6周龄SD大鼠，根据简单随机法分为3组：对照组(

=5)、安慰剂组(

=5)与BAPN组(

=5)，对照组作空白对照，安慰剂组与BAPN组分别在大鼠尾椎原位注射20 μL PBS缓冲液或BAPN(100 μg/mL)，术后2周及4周拍摄X线评估椎间盘退变情况。

结果

X线证实随着年龄的增加，20月龄大鼠椎间盘高度与2月龄相比明显下降(

0.01)，MRI中T2信号降低，出现退变性状；20月龄大鼠椎间盘中LOX蛋白量明显减少(

0.01)；髓核细胞在300 mmol/L CoCl

诱导的严重缺氧环境中发生凋亡(

0.05)，同时LOX表达下调(

0.05)，进一步抑制LOX蛋白表达后凋亡增加(

0.05)；体内实验表明，用BAPN抑制LOX蛋白功能后4周，BAPN组大鼠椎间盘高度下降明显比安慰剂组严重(

0.01)，退变程度加重。

结论

LOX蛋白可以调控缺氧诱导的髓核细胞的凋亡进而影响椎间盘退变。

Abstract

Objective

To explore the role and possible mechanism of lysyl oxidase (LOX) in age-related degeneration of intervertebral disc.

Methods

Six SD rats

aged of 2

8 and 20 months respectively

were subjected

and then underwent intervertebral disc MRI and X-ray to evaluate the effect of age on intervertebral disc degeneration. Then

the total proteins of intervertebral disc from different age groups were isolated and detected for the expression of LOX protein by Western blotting. The hypoxia apoptosis model of nucleus pulposus cells was established by CoCl

treatment. Through LOX protein inhibitor BAPN and plasmid pcDNA3.1 (+)-LOX

the effect of LOX protein on apoptosis of nucleus pulposus cells under different hypoxia conditions was studied. Fifteen 6-week-old SD rats were randomly divided into blank control group

vehicle group and BAPN group

with 5 animals in each group. PBS buffer of 20 μL or BAPN of 100 μg/mL was injected into the rats from the vehicle or BAPN group

via

caudal vertebrae. X-ray film examination was taken at 2 and 4 weeks after operation to evaluate intervertebral disc degeneration.

Results

With the increase of age

X-ray films showed that the intervertebral disc height of 20-month-old rats was decreased significantly compared with 2-month-old rats (

0.01)

and MRI displayed reduced T2 signals

indicating appearance of intervertebral disc degeneration. The protein level of LOX was decreased significantly in intervertebral disc of 20-month-old rats (

0.01). Treatment of 300 mmol/L CoCl

induced obvious apoptosis of nucleus pulposus cells as severe hypoxic condition (

0.05) and subsequently down-regulated the expression of LOX protein (

0.05).

In vivo

experiment showed that after LOX inhibitor BAPN treatment for 4 weeks

the height of intervertebral disc was significantly declined in the BAPN group when compared with the PBS group (

0.01)

suggesting more serious degeneration of int

ervertebral disc.

Conclusion

LOX protein can regulate the apoptosis of nucleus pulposus cells induced by hypoxia and thus affect intervertebral disc degeneration.

关键词

Keywords

references

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