Injectable and tissue adhesive EGCG-laden hyaluronic acid hydrogel depot for treating oxidative stress and inflammation.

Oxidative stress has been proved to play important roles in the development of intervertebral disc degeneration (IDD); however, the underlying mechanism remains obscure to date. The aim of this study was to elucidate the vital roles of oxidative stress-related genes in the development of IDD using strict bioinformatic algorithms. The microarray data relevant to the IDD was downloaded from Gene Expression Omnibus database for further analysis. A series of bioinformatic strategies were used to determine the oxidative stress-related and IDD-related genes (OSIDDRGs), perform the function enrichment analysis and protein-protein interaction analysis, construct the lncRNA-miRNA-mRNA regulatory network, and investigate the potential relationship of oxidative stress to immunity abnormality and autophagy in IDD. We observed a significantly different status of oxidative stress between normal intervertebral disc tissues and IDD tissues. A total of 72 OSIDDRGs were screened out for the further function enrichment analysis, and 10 hub OSIDDRGs were selected to construct the lncRNA-miRNA-mRNA regulatory network. There was a very close association of oxidative stress with immunity abnormality and autophagy in IDD. Taken together, our findings can provide new insights into the mechanism research of oxidative stress in the development of IDD and offer new potential targets for the treatment strategies.

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Oxidative Stress in Intervertebral Disc Degeneration: New Insights from Bioinformatic Strategies

Low back pain is a major cause of disability worldwide that declines the quality of life; it poses a substantial economic burden for the patient and society. Intervertebral disc (IVD) degeneration (IDD) is the main cause of low back pain, and it is also the pathological basis of several spinal degenerative diseases, such as intervertebral disc herniation and spinal stenosis. The current clinical drug treatment of IDD focuses on the symptoms and not their pathogenesis, which results in frequent recurrence and gradual aggravation. Moreover, the side effects associated with the long-term use of these drugs further limit their use. The pathological mechanism of IDD is complex, and oxidative stress and inflammation play an important role in promoting IDD. They induce the destruction of the extracellular matrix in IVD and reduce the number of living cells and functional cells, thereby destroying the function of IVD and promoting the occurrence and development of IDD. Phytochemicals from fruits, vegetables, grains, and other herbs play a protective role in the treatment of IDD as they have anti-inflammatory and antioxidant properties. This article reviews the protective effects of phytochemicals on IDD and their regulatory effects on different molecular pathways related to the pathogenesis of IDD. Moreover, the therapeutic limitations and future prospects of IDD treatment have also been reviewed. Phytochemicals are promising candidates for further development and research on IDD treatment.

/pdf/targeting-oxidative-stress-and-inflammation-in-6wa14pd4.pdf

Targeting Oxidative Stress and Inflammation in Intervertebral Disc Degeneration: Therapeutic Perspectives of Phytochemicals

Intervertebral disc degeneration (IVDD) is a common pathological condition responsible for lower back pain, which can significantly increase economic and social burdens. Although considerable efforts have been made to identify potential mechanisms of disc degeneration, the treatment of IVDD is not satisfactory. Ferroptosis, a recently reported form of regulated cell death (RCD), is characterized by iron-dependent lipid peroxidation and has been demonstrated to be responsible for a variety of degenerative diseases. Accumulating evidence suggests that ferroptosis is implicated in IVDD by decreasing viability and increasing extracellular matrix degradation of nucleus pulposus cells, annulus fibrosus cells, or endplate chondrocytes. In this review, we summarize the literature regarding ferroptosis of intervertebral disc cells and discuss its molecular pathways and biomarkers for treating IVDD. Importantly, ferroptosis is verified as a promising therapeutic target for IVDD.

/pdf/targeting-ferroptosis-holds-potential-for-intervertebral-3uqq2gl8.pdf

Targeting Ferroptosis Holds Potential for Intervertebral Disc Degeneration Therapy

Low back pain (LBP) is a chronic condition that causes great individual suffering and economic burden. The major contributor of LBP is intervertebral disc degeneration (IDD), which is caused by a spectrum of homeostasis alteration, including the apoptosis of nucleus pulposus (NP) and annulus fibrosus (AF) cells, degradation of extracellular matrix (ECM), calcification of cartilaginous endplates (CEP) and so on. Currently, the therapeutic strategy for IDD includes conservative and surgery treatment. Nevertheless, none of them could reverse the progressive destruction of the intervertebral disc. Hence, it is pivotal to pursue a new therapeutic approach. Exosomes, nano-sized substances with diameters of 30-150 nm, can be synthesized and secreted by various types of cells. They play an important role in intercellular communication. Increasing evidence implicates that exosomes could impact the intracellular transcription activities, thereby inhibiting or accelerating the proliferation and apoptosis of cells. Thus, it is a new therapeutic source for IDD. This review chiefly focuses on generalizing and clarifying the roles of exosomes in the onset and deterioration of IDD, and their therapeutic potential.

Insights into Exosome in the Intervertebral Disc: Emerging Role for Disc Homeostasis and Normal Function

Intervertebral disc degeneration is a very common type of degenerative disease causing severe socioeconomic impact, as well as a major cause of discogenic low back pain and herniated discs, placing a heavy burden on patients and the clinicians who treat them. IDD is known to be associating with a complex process involving in extracellular matrix and cellular damage, and in recent years, there is increasing evidence that oxidative stress is an important activation mechanism of IDD and that reactive oxygen and reactive nitrogen species regulate matrix metabolism, proinflammatory phenotype, autophagy and senescence in intervertebral disc cells, apoptosis, autophagy, and senescence. Despite the tremendous efforts of researchers within the field of IDD pathogenesis, the proven strategies to prevent and treat this disease are still very limited. Up to now, several antioxidants have been proved to be effective for alleviating IDD. In this article, we discussed that oxidative stress accelerates disc degeneration by influencing aging, inflammation, autophagy, and DNA methylation, and summarize some antioxidant therapeutic measures for IDD, indicating that antioxidant therapy for disc degeneration holds excellent promise.

/pdf/the-role-of-oxidative-stress-in-intervertebral-disc-2fl2tvaf.pdf

Jianye Cao

Papers

The Role of Oxidative Stress in Intervertebral Disc Degeneration