The involvement of regulated in development and DNA damage response 1 (REDD1) in the pathogenesis of intervertebral disc degeneration
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 (China)
Regulated in development and DNA damage response 1 (REDD1) is an evolutionarily conserved, ubiquitous protein that responds to various cell stresses. Studies have proved REDD1 is involved in many diseases, such as osteoarthritis and cancer. The present study aimed to investigate the potential role of REDD1 in the pathogenesis of intervertebral disc degeneration (IDD). Analysis of clinical tissue samples showed REDD1 expression was up-regulated during IDD and was correlated with the grade of disc degeneration. Overexpression of REDD1 in normal human nucleus pulposus (NP) cells resulted in extracellular matrix (ECM) degeneration. Further, we investigated the function of REDD1 using a serum deprivation-induced IDD vitro model and found that REDD1 was up-regulated in a temporal manner. However, hypoxia abolished this increase through down-regulation of NF-κB. Knockdown of REDD1 or NF-κB by si-RNA significantly rescued ECM from degeneration both in normoxia and hypoxia. In addition, NF-κB/REDD1 mediated the protection of hypoxia from serum deprivation-induced apoptosis and autophagy in NP cells. These results suggest that REDD1 might play a pivotal role in IDD pathogenesis, thereby potentially providing a new therapeutic target for IDD treatment.
- OSTI ID:
- 23082346
- Journal Information:
- Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 372; ISSN 0014-4827; ISSN ECREAL
- Country of Publication:
- United States
- Language:
- English
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