机构：[1]Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310053, Zhejiang, China[2]Hangzhou Fuyang Hospital of TCM Orthopedics and Traumatology,Hangzhou 311400, Zhejiang, China[3]Department of Pharmacy, the Second Affiliated Hospital, Zhejiang UniversitySchool of Medicine, Hangzhou 310009, Zhejiang, China[4]Research Institute of Orthopedics, the Affiliated JiangNanHospital of Zhejiang Chinese Medical University, Hangzhou 311200, Zhejiang, China[5]Longhua Hospital, Affiliatedto Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China[6]Department of Orthopedics,Shenzhen Traditional Chinese Hospital, Guangzhou University of Chinese Medicine, Shenzhen 518055,China深圳市康宁医院深圳医学信息中心[7]Department of Physiology, Zhejiang Chinese Medical University, Hangzhou 310053, China[8]ResearchCenter for Human Tissues and Organs Degeneration, Shenzhen Institutes of Advanced Technology, ChineseAcademy of Sciences, Shenzhen 518055, China[9]The First Clinical College, Zhejiang Chinese Medical University,Hangzhou 310051, Zhejiang, China
Aberrant mechanical factor is one of the etiologies of the intervertebral disc (IVD) degeneration (IVDD). However, the exact molecular mechanism of spinal mechanical loading stress-induced IVDD has yet to be elucidated due to a lack of an ideal and stable IVDD animal model. The present study aimed to establish a stable IVDD mouse model and evaluated the effect of aberrant spinal mechanical loading on the pathogenesis of IVDD. Eight-week-old male mice were treated with lumbar spine instability (LSI) surgery to induce IVDD. The progression of IVDD was evaluated by μCT and Safranin O/Fast green staining analysis. The metabolism of extracellular matrix, ingrowth of sensory nerves, pyroptosis in IVDs tissues were determined by immunohistological or real-time PCR analysis. The apoptosis of IVD cells was tested by TUNEL assay. IVDD modeling was successfully produced by LSI surgery, with substantial reductions in IVD height, BS/TV, Tb.N. and lower IVD score. LSI administration led to the histologic change of disc degeneration, disruption of the matrix metabolism, promotion of apoptosis of IVD cells and invasion of sensory nerves into annulus fibrosus, as well as induction of pyroptosis. Moreover, LSI surgery activated Wnt signaling in IVD tissues. Mechanical instability caused by LSI surgery accelerates the disc matrix degradation, nerve invasion, pyroptosis, and eventually lead to IVDD, which provided an alternative mouse IVDD model.
基金：
This study was finacially supported by National Natural Science Foundation of China (Nos: 81804121, 81973870, 81904053, 81973877, 81573994 and 81674006), China Postdoctoral Science Foundation (No.: 2018M632154), Natural Science Foundation of Zhejiang Province (Nos.: LY19H270006, LY19H290004 and LQ17H270005), Traditional Chinese Medical Administration of Zhejiang Province (Nos.: 2021ZB090 and 2017ZB026), Zhejiang medical and health science and technology project (Nos.: 2018269058 and 2021ZB090), Zhejiang Chinese Medical University Scientific Research Fund Project (No.: 2018ZG20), Postgraduate Science Research Fund of Zhejiang Chinese Medical University (2020YKJ07), National Undergraduate Innovation and Entrepreneurship Training Program (202010344004), Opening Project of Zhejiang Provincial Preponderant and Characteristic Subject of Key University (Chinese Traditional Medicine) and Zhejiang Chinese Medical University (No.: ZYX2018008), Plan Guide Project of HangZhou Technology Department (No.: 20171226Y98), Plan technology project of Hangzhou Health Department (No.: 2018B028), Science and Technology Innovation Program for College Students (New talent program) of Zhejiang Province (No.: 2018R410030).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|3 区综合性期刊
小类|3 区综合性期刊
最新[2025]版：
大类|3 区综合性期刊
小类|3 区综合性期刊
第一作者：
第一作者机构：[1]Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310053, Zhejiang, China[9]The First Clinical College, Zhejiang Chinese Medical University,Hangzhou 310051, Zhejiang, China
共同第一作者：
通讯作者：
通讯机构：[1]Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310053, Zhejiang, China[5]Longhua Hospital, Affiliatedto Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
推荐引用方式(GB/T 7714)：
Fangda Fu,Ronghua Bao,Sai Yao,et al.Aberrant spinal mechanical loading stress triggers intervertebral disc degeneration by inducing pyroptosis and nerve ingrowth.[J].Scientific reports.2021,11(1):772.doi:10.1038/s41598-020-80756-6.
