Hydrostatic Pressure Modulates Intervertebral Disc Cell Survival and Extracellular Matrix Homeostasis via Regulating Hippo-YAP/TAZ Pathway

作者全名："Wang, Yiyang; Bai, Baoshuai; Hu, Yanzhu; Wang, Haoming; Liu, Ningyuan; Li, Yibo; Li, Pei; Zhou, Guangdong; Zhou, Qiang"

作者地址："[Wang, Yiyang; Hu, Yanzhu; Liu, Ningyuan; Li, Pei; Zhou, Qiang] Chongqing Med Univ, Dept Orthoped, Affiliated Hosp 3, Chongqing 401120, Peoples R China; [Wang, Yiyang; Hu, Yanzhu; Wang, Haoming; Liu, Ningyuan; Li, Pei; Zhou, Qiang] Chongqing Med Univ, Tissue Repairing & Biotechnol Res Ctr, Affiliated Hosp 3, Chongqing 401120, Peoples R China; [Wang, Yiyang; Bai, Baoshuai; Zhou, Guangdong] Natl Tissue Engn Ctr China, Shanghai 200241, Peoples R China; [Bai, Baoshuai; Zhou, Guangdong] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Plast & Reconstruct Surg, Shanghai Key Lab Tissue Engn,Sch Med, Shanghai 200011, Peoples R China; [Bai, Baoshuai; Zhou, Guangdong] Wei Fang Med Coll, Res Inst Plast Surg, Wei Fang 261053, Peoples R China; [Wang, Haoming] Chongqing Univ, Three Gorges Cent Hosp, Dept Orthoped, Chongqing 404000, Peoples R China; [Li, Yibo] Gen Hosp Cent Theater Command, Dept Orthoped, Wuhan 430000, Peoples R China"

通信作者："Li, P; Zhou, Q (corresponding author), Chongqing Med Univ, Dept Orthoped, Affiliated Hosp 3, Chongqing 401120, Peoples R China.; Li, P; Zhou, Q (corresponding author), Chongqing Med Univ, Tissue Repairing & Biotechnol Res Ctr, Affiliated Hosp 3, Chongqing 401120, Peoples R China.; Zhou, GD (corresponding author), Natl Tissue Engn Ctr China, Shanghai 200241, Peoples R China.; Zhou, GD (corresponding author), Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Plast & Reconstruct Surg, Shanghai Key Lab Tissue Engn,Sch Med, Shanghai 200011, Peoples R China.; Zhou, GD (corresponding author), Wei Fang Med Coll, Res Inst Plast Surg, Wei Fang 261053, Peoples R China."

来源：STEM CELLS INTERNATIONAL

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000669919200001

JCR分区：Q3

影响因子：4.3

年份：2021

卷号：2021

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Established studies proved that hydrostatic pressure had multiple effects on the biological behavior of the intervertebral disc (IVD). However, the conclusions of the previous studies were inconsistent, due to the difference in hydrostatic loading devices and observing methods used in these studies. The current study is aimed at investigating the role of dynamic hydrostatic pressure in regulating biological behavior of the notochordal nucleus pulposus (NP) and fibrocartilaginous inner annulus fibrosus (AF) and its possible mechanism using our novel self-developed hydrostatic pressure bioreactor. The differences in the biological behavior of the rabbit IVD tissues under different degree of hydrostatic pressure were evaluated via histological analysis. Results revealed that low-loading dynamic hydrostatic pressure was beneficial for cell survival and extracellular matrix (ECM) homeostasis in notochordal NP and fibrocartilaginous inner AF via upregulating N-cadherin (N-CDH) and integrin beta 1. In comparison, high-magnitude dynamic hydrostatic pressure aggravated the breakdown of ECM homeostasis in NP and inner AF via enhancing the Hippo-YAP/TAZ pathway-mediated cell apoptosis. Moreover, inner AF exhibited greater tolerance to physiological medium-loading degree of hydrostatic pressure than notochordal NP. The potential mechanism was related to the differential expression of mechanosensing factors in notochordal NP and fibrocartilaginous inner AF, which affects the fate of the cells under hydrostatic pressure. Our findings may provide a better understanding of the regulatory role of hydrostatic pressure on the cellular fate commitment and matrix metabolism of the IVD and more substantial evidence for using hydrostatic pressure bioreactor in exploring the IVD degeneration mechanism as well as regeneration strategies."

基金机构："National Key R&D Program of China [2018YFC1105803]; Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81772378, 81974346]; Natural Science Foundation of Chongqing, ChinaNatural Science Foundation of Chongqing [cstc2020jcyj-msxmX0148]; Basic Research and Frontier Exploration Project of Yuzhong District, Chongqing, China [20200121]; Project of Innovative Science Research for Postgraduate of Chongqing Municipal Education Committee, Chongqing, China [CYB20168, CYS20226]; Basic Research Incubation Project of the Third Affiliated Hospital of Chongqing Medical University, Chongqing, China [KY20077]"

基金资助正文："We sincerely thank Dr. Yujie Hua, Dr. Erji Gao, Dr. Xintong Zhao, Dr. Zheng Ci, Dr. Tao Wang, Dr. Wei Xu, and Dr. Xiaodi Wu from the National Tissue Engineering Center of China for their generous technical assistance. This work was supported by grants from the National Key R&D Program of China (No. 2018YFC1105803); the Natural Science Foundation of China (No. 81772378, No. 81974346); the Natural Science Foundation of Chongqing, China (No. cstc2020jcyj-msxmX0148); the Basic Research and Frontier Exploration Project of Yuzhong District, Chongqing, China (No. 20200121); the Project of Innovative Science Research for Postgraduate of Chongqing Municipal Education Committee, Chongqing, China (CYB20168, CYS20226); and the Basic Research Incubation Project of the Third Affiliated Hospital of Chongqing Medical University, Chongqing, China (No. KY20077)."