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Decorin inhibits nucleus pulposus apoptosis by matrix‐induced autophagy via the mTOR pathway
Author(s) -
Zhang TaiWei,
Li ZeFang,
Ding Wang,
Wang HuiRen,
Ding ShengLong,
Han GuanJie,
Li XiLei,
Dong Jian,
Jiang LiBo
Publication year - 2021
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.24882
Subject(s) - autophagy , pi3k/akt/mtor pathway , decorin , microbiology and biotechnology , chemistry , small interfering rna , matrix metalloproteinase 3 , apoptosis , terminal deoxynucleotidyl transferase , western blot , signal transduction , nucleus , aggrecan , tunel assay , proteoglycan , matrix metalloproteinase , biology , biochemistry , rna , extracellular matrix , medicine , gene , articular cartilage , alternative medicine , pathology , osteoarthritis
Decorin (Dcn) is a member of the class I small leucine‐rich proteoglycans, whose expression in the nucleus pulposus (NP) of intervertebral discs (IVDs) has been shown to increase with aging in humans and sheep. Dcn induces autophagy in endothelial cells; however, its precise role in NP and IVD degeneration during aging is not well understood. We addressed this question in the present study by treating rat nucleus pulposus cells (NPCs) with different concentrations of Dcn. The Western blot analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling assay results showed that Dcn treatment induced autophagy and decreased apoptosis caused by interleukin (IL)‐1β application. This effect was dependent on the protein kinase B/mechanistic target of rapamycin (mTOR)/p70 S6 kinase signaling. Dcn treatment also decreased the expression of matrix metalloproteinase‐3 and ‐13 and decreased the IL‐1β‐induced attenuation of collagen type II and aggrecan levels. The role of Dcn in stimulating autophagy was further supported by the fact that the observed effects were abrogated by knocking down autophagy‐related protein 7 with Atg7 small interfering RNA. Thus, Dcn protects NPCs in IVDs from IL‐1β‐induced apoptosis and degeneration by promoting autophagy through mTOR signaling.