Abstract
Intervertebral disc degeneration (IVDD) is a pathological condition that can lead to intractable back pain or secondary neurological deficits. There is no fundamental cure for this condition, and current treatments focus on alleviating symptoms indirectly. Numerous studies have been performed to date, and the major strategy for all treatments of IVDD is to prevent cell loss due to programmed or regulated cell death. Accumulating evidence suggests that several types of cell death other than apoptosis, including necroptosis, pyroptosis, and ferroptosis, are also involved in IVDD. In this study, we discuss the molecular pathway of each type of cell death and review the literature that has identified their role in IVDD. We also summarize the recent advances in targeted therapy at the RNA level, including RNA modulations through RNA interference and regulation of non-coding RNAs, for preventing cell death and subsequent IVDD. Therefore, we review the causes and possible therapeutic targets for RNA intervention and discuss the future direction of this research field.
Highlights
Academic Editor: Alexander E.Intervertebral discs are located between the vertebrae and confer mobility, load absorbability, and support to the spinal unit [1]
We review the molecular signaling pathways of PRCD and molecular targets to suppress these types of cell death, focusing on mRNA interference and modulation of ncRNAs, thereby inhibiting the progression of Intervertebral disc degeneration (IVDD)
HLA complex group 18 (HCG18) is another long ncRNAs (lncRNAs) that has been found to be upregulated in nucleus pulposus (NP) tissues from herniated or bulging discs [124,126]; HCG18 acts as an endogenous sponge for miR-146a-5p to inhibit cell proliferation, promote apoptosis, and enhance the release of chemoattractants for macrophages in NP cells [124,126]
Summary
The mechanism through which IVDD contributes to low back pain is not fully understood; several studies have reported the role of aggrecans in nerve and/or blood vessel ingrowth that can be attributed to the generation of nociceptive and neuropathic pain signals. The molecular mechanism underlying IVDD includes DNA replication error, metabolic disorder, and inflammation, and the consequent loss of the disc matrix, functional cells, and stem cells is a characteristic of degenerated discs. Autophagy stimulated by hypoxia or metformin exhibited a protective effect against apoptosis of NP cells [31,34] These previous studies underscore the complex role of autophagy in the development of IVDD, indicating that the regulation of autophagy may be an approach for IVDD treatments. We review the molecular signaling pathways of PRCD and molecular targets to suppress these types of cell death, focusing on mRNA interference and modulation of ncRNAs, thereby inhibiting the progression of IVDD
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