N-cadherin Alleviates Apoptosis and Senescence of Nucleus Pulposus Cells via Suppressing ROS-dependent ERS in the Hyper-osmolarity Microenvironment

作者全名："Zou, Luetao; Wang, Yiyang; Hu, Yanzhu; Liu, Liehua; Luo, Lei; Chen, Zhao; Zhuo, Yunyun; Li, Pei; Zhou, Qiang"

作者地址："[Zou, Luetao; Wang, Yiyang; Hu, Yanzhu; Liu, Liehua; Luo, Lei; Chen, Zhao; Zhuo, Yunyun; Li, Pei; Zhou, Qiang] Chongqing Med Univ, Affiliated Hosp 3, Dept Orthoped, Chongqing 400010, Peoples R China; [Li, Pei; Zhou, Qiang] Chongqing Med Univ, Affiliated Hosp 3, Dept Orthoped, Chongqing 400010, Peoples R China"

通信作者："Li, P; Zhou, Q (通讯作者)，Chongqing Med Univ, Affiliated Hosp 3, Dept Orthoped, Chongqing 400010, Peoples R China."

来源：INTERNATIONAL JOURNAL OF MEDICAL SCIENCES

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001174448600009

JCR分区：Q1

影响因子：3.6

年份：2024

卷号：21

期号：2

开始页：341

结束页：356

文献类型：Article

关键词：N-cadherin; nucleus pulposus cells; intervertebral disc degeneration; endoplasmic reticulum stress; hyper-osmolarity microenvironment

摘要："The in-situ osmolarity is an important physicochemical factor that regulates cell fate of nucleus pulposus cells (NPCs). Our previous studies demonstrated that reduced N-cadherin (NCDH) expression in nucleus pulposus cells is associated with cellular damage under hyper-osmolarity microenvironment. This study was aimed at exploring the impacts of NCDH on senescence and apoptosis of NPCs, as well as the potential molecular mechanism. By comparing NPCs from patients with lumbar fractures and lumbar disc herniation, we identified a correlation between decreased NCDH expression and increased endoplasmic reticulum stress (ERS), resulting in undesirable cell fate (senescence and apoptosis). After blocking Reactive oxygen species (ROS) or ERS, it was indicated that hyper-osmolarity microenvironment induced ERS was ROS-dependent. Further results demonstrated the correlation in rat NPCs. Upregulation of NCDH expression reduced ROS-dependent ERS, thus limiting undesirable cell fates in vitro. This was further confirmed through the rat tail acupuncture injection model. NCDH overexpression successfully mitigated ERS, preserved extracellular matrix production and alleviating intervertebral disc degeneration in vivo. Together, NCDH can alleviate senescence and apoptosis of NPCs by suppressing ROS-dependent ERS via the ATF4-CHOP signaling axis in the hyper-osmolarity microenvironment, thus highlighting the therapeutic potential of NCDH in combating degenerative disc diseases."

基金机构："Basic Research and Frontier Exploration Project of Yuzhong District, Chongqing, China [20200121]; National Natural Science Foundation of China [81974346]; Natural Science Foundation of Chongqing, China [cstc2020jcyj-msxmX0148]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN20210 0426]; Basic Research Incubation Project of the Third Affiliated Hospital of Chongqing Medical University, Chongqing, China [KY20077]"

基金资助正文："This study was funded by Basic Research and Frontier Exploration Project of Yuzhong District, Chongqing, China (No. 20200121) . The National Natural Science Foundation of China (No.81974346) . Natural Science Foundation of Chongqing, China (No. cstc2020jcyj-msxmX0148) . The Science and Technology Research Program of Chongqing Municipal Education Commission (No. KJQN20210 0426) . Basic Research Incubation Project of the Third Affiliated Hospital of Chongqing Medical University, Chongqing, China (No. KY20077) ."