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Fibronectin induced ITGβ1/FAK‐dependent apoptotic pathways determines the fate of degenerative NP cells
Author(s) -
Wu Xinghuo,
Wang Kun,
Hua Wenbin,
Li Shuai,
Liu Xianzhe,
Song Yu,
Zhang Yukun,
Shao Zengwu,
Li Suyun,
Yang Cao
Publication year - 2019
Publication title -
journal of orthopaedic research®
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.24169
Subject(s) - anoikis , focal adhesion , fibronectin , microbiology and biotechnology , apoptosis , extracellular matrix , integrin , gene knockdown , signal transduction , chemistry , protein kinase b , downregulation and upregulation , bcl xl , biology , programmed cell death , cell , biochemistry , gene
Intervertebral disc (IVD) degeneration is caused by a decrease in nucleus pulposus (NP) cells, due mainly to apoptosis. Focal adhesion kinase (FAK) is involved in the integrin (ITG)‐mediated control of cell adhesion and anoikis (apoptosis). To explore the involvement of ITGβ1/FAK‐dependent apoptotic pathways in disc degeneration, histological, and molecular biological studies on the protein expression of fibronectin (FN), ITGβ1, and syndecan 4 (SYND4) in non‐degenerative and degenerative NP tissues were conducted. Degenerative NP cells were isolated and cultured in the presence of SYND4 and/or ITGβ1, with or without an FAK inhibitor. The effects of upregulation or knockdown of ITGβ1 gene expression were also examined. The TUNEL assay was used to determine the percentage of apoptotic cells. Western blotting was used to detect the expression of SYND4, ITGβ1, FAK, and downstream pathway proteins. The results showed that extracellular FN was degraded during the IVD degeneration process, detrimentally affecting the function, and survival of NP cells. The apoptotic rate was increased by ITGβ1 activation, but partially reduced by FN. After ITGβ1 knockdown, the FAK/PI3 K/AKT axis was activated in the ITGβ1/FAK‐dependent pathways, resulting in increased cell adherence capacity and decreased anoikis. FN rescued the degenerative NP cells from anoikis through the FAK‐dependent signaling pathways. In conclusion, the extracellular matrix protein FN is essential for maintaining the function and survival of NP cells through ITGβ1/FAK‐dependent apoptotic pathways during disc degeneration. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:439–448, 2019.