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Optical Sectioning and Visualization of the Intervertebral Disc from Embryonic Development to Degeneration
Published on: July 8, 2021
The involvement of regulated in development and DNA damage response 1 (REDD1) in the pathogenesis of intervertebral
Huipeng Yin1, Yukun Zhang1, Kun Wang1
1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Abstract:
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.
Insights
Regulated in development and DNA damage response 1 (REDD1) protein is elevated in intervertebral disc degeneration (IDD). REDD1 contributes to extracellular matrix damage, offering a potential therapeutic target for IDD.
Area of Science:
- Biochemistry
- Cell Biology
- Pathology
Background:
- Regulated in development and DNA damage response 1 (REDD1) is a stress-responsive protein implicated in various diseases.
- Intervertebral disc degeneration (IDD) is a debilitating condition with complex underlying mechanisms.
Purpose of the Study:
- To investigate the role of REDD1 in the pathogenesis of intervertebral disc degeneration (IDD).
Main Methods:
- Analysis of clinical tissue samples from IDD patients.
- Overexpression and knockdown studies in human nucleus pulposus (NP) cells.
- In vitro IDD models under normoxia and hypoxia.
- Assessment of extracellular matrix (ECM) degeneration, apoptosis, and autophagy.
- Investigation of the NF-κB signaling pathway.
Main Results:
- REDD1 expression is upregulated in IDD and correlates with disease severity.
- REDD1 overexpression induces ECM degeneration in NP cells.
- Hypoxia downregulates REDD1 via NF-κB, but REDD1 knockdown rescues ECM.
- The NF-κB/REDD1 pathway mediates protection against apoptosis and autophagy in NP cells.
Conclusions:
- REDD1 plays a significant role in IDD pathogenesis.
- Targeting REDD1 presents a potential therapeutic strategy for IDD treatment.
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