LncRNA LINC00324 is upregulated in intervertebral disk degeneration and upregulates FasL in nucleus pulposus cells

Abstract Background Adjacent segmental intervertebral disk degeneration (ASDD) is a major complication secondary to lumbar fusion. Although ASSD pathogenesis remains unclear, the primary cause of intervertebral disk degeneration (IVDD) development is apoptosis of nucleus pulposus (NP). Raloxifene (RAL) could delay ASDD by inhibiting NP apoptosis. Methods An ASDD rat model was established by ovariectomy (OVX) and posterolateral spinal fusion (PLF) on levels 4–5 of the lumbar vertebrae. Rats in the treatment groups were administered 1 mg/kg/d RAL by gavage for 12 weeks, following which, all animals were euthanized. Lumbar fusion, apoptosis, ASDD, and vertebrae micro-architecture were evaluated. Results RAL maintained intervertebral disk height (DHI), delayed vertebral osteoporosis, reduced histological score, and inhibited apoptosis. The OVX+PLF+RAL group revealed upregulated expression of aggrecan and B-cell lymphoma-2 (bcl2), as well as significantly downregulated expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), metalloproteinase-13 (MMP-13), caspase-3, BCL2-associated X (bax), and transferase dUTP nick end labeling (TUNEL) staining. Micro-computed tomography (Micro-CT) analysis revealed higher bone volume fraction (BV/TV), bone mineral density (BMD), and trabecular number (Tb.N), and lower trabecular separation (Tb.Sp) in OVX+PLF+RAL group than in the OVX+PLF group. Conclusions RAL can postpone ASDD development in OVX rats through inhibiting extracellular matrix metabolic imbalance, NP cell apoptosis, and vertebral osteoporosis. These findings showed RAL as a potential therapeutic target for ASDD.

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Circ_0040039 May Aggravate Intervertebral Disk Degeneration by Regulating the MiR-874-3p-ESR1 Pathway

Frontiers in Genetics ◽

10.3389/fgene.2021.656759 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yongjin Li ◽

Xuke Wang ◽

Haiwei Xu ◽

Guowang Li ◽

Zhenxin Huo ◽

...

Keyword(s):

Interaction Network ◽

Intervertebral Disk ◽

Circular Rnas ◽

Ppi Network ◽

Nucleus Pulposus Cells ◽

Protein Protein Interaction ◽

Intervertebral Disk Degeneration ◽

Disk Degeneration ◽

Esr1 Expression ◽

Functional Alteration

The functional alteration of nucleus pulposus cells (NPCs) exerts a crucial role in the occurrence and progression of intervertebral disk degeneration (IDD). Circular RNAs and microRNAs (miRs) are critical regulators of NPC metabolic processes such as growth and apoptosis. In this study, bioinformatics tools, encompassing Gene Ontology pathway and Venn diagrams analysis, and protein–protein interaction (PPI) network construction were used to identify functional molecules related to IDD. PPI network unveiled that ESR1 was one of the most critical genes in IDD. Then, a key IDD-related circ_0040039-miR-874-3p-ESR1 interaction network was predicted and constructed. Circ_0040039 promoted miR-874-3p and repressed ESR1 expression, and miR-874-3p repressed ESR1 expression in NPCs, suggesting ESR1 might be a direct target of miR-874-3p. Functionally, circ_0040039 could enhance NPC apoptosis and inhibit NPC growth, revealing that circ_0040039 might aggravate IDD by stabilizing miR-874-3p and further upregulating the miR-874-3p-ESR1 pathway. This signaling pathway might provide a novel therapeutic strategy and targets for the diagnosis and therapy of IDD-related diseases.

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Bu‐Shen‐Huo‐Xue‐Fang modulates nucleus pulposus cell proliferation and extracellular matrix remodeling in intervertebral disk degeneration through miR‐483 regulation of Wnt pathway

Journal of Cellular Biochemistry ◽

10.1002/jcb.26760 ◽

2019 ◽

Vol 120 (12) ◽

pp. 19318-19329 ◽

Cited By ~ 3

Author(s):

Shaofeng Yang ◽

Linghui Li ◽

Liguo Zhu ◽

Chao Zhang ◽

Zhaoyong Li ◽

...

Keyword(s):

Extracellular Matrix ◽

Cell Proliferation ◽

Nucleus Pulposus ◽

Wnt Pathway ◽

Nucleus Pulposus Cell ◽

Intervertebral Disk ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Intervertebral Disk Degeneration ◽

Disk Degeneration

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Advances and Prospects in Biomaterials for Intervertebral Disk Regeneration

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.766087 ◽

2021 ◽

Vol 9 ◽

Author(s):

Chunxu Li ◽

Qiushi Bai ◽

Yuxiao Lai ◽

Jingjing Tian ◽

Jiahao Li ◽

...

Keyword(s):

Tissue Engineering ◽

Nucleus Pulposus ◽

Cell Transplantation ◽

Annulus Fibrosus ◽

Functional Polymers ◽

Intervertebral Disk ◽

Fusion Surgery ◽

Intervertebral Disk Degeneration ◽

Disk Degeneration ◽

Intervertebral Disks

Low-back and neck-shoulder pains caused by intervertebral disk degeneration are highly prevalent among middle-aged and elderly people globally. The main therapy method for intervertebral disk degeneration is surgical intervention, including interbody fusion, disk replacement, and diskectomy. However, the stress changes caused by traditional fusion surgery are prone to degeneration of adjacent segments, while non-fusion surgery has problems, such as ossification of artificial intervertebral disks. To overcome these drawbacks, biomaterials that could endogenously regenerate the intervertebral disk and restore the biomechanical function of the intervertebral disk is imperative. Intervertebral disk is a fibrocartilaginous tissue, primarily comprising nucleus pulposus and annulus fibrosus. Nucleus pulposus (NP) contains high water and proteoglycan, and its main function is absorbing compressive forces and dispersing loads from physical activities to other body parts. Annulus fibrosus (AF) is a multilamellar structure that encloses the NP, comprises water and collagen, and supports compressive and shear stress during complex motion. Therefore, different biomaterials and tissue engineering strategies are required for the functional recovery of NP and AF based on their structures and function. Recently, great progress has been achieved on biomaterials for NP and AF made of functional polymers, such as chitosan, collagen, polylactic acid, and polycaprolactone. However, scaffolds regenerating intervertebral disk remain unexplored. Hence, several tissue engineering strategies based on cell transplantation and growth factors have been extensively researched. In this review, we summarized the functional polymers and tissue engineering strategies of NP and AF to endogenously regenerate degenerative intervertebral disk. The perspective and challenges of tissue engineering strategies using functional polymers, cell transplantation, and growth factor for generating degenerative intervertebral disks were also discussed.

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The long noncoding RNA SNHG1 promotes nucleus pulposus cell proliferation through regulating miR-326 and CCND1

AJP Cell Physiology ◽

10.1152/ajpcell.00220.2017 ◽

2018 ◽

Vol 315 (1) ◽

pp. C21-C27 ◽

Cited By ~ 10

Author(s):

Hongyu Tan ◽

Liang Zhao ◽

Ruipeng Song ◽

Yilin Liu ◽

Limin Wang

Keyword(s):

Cell Proliferation ◽

Cyclin D1 ◽

Nucleus Pulposus ◽

Noncoding Rna ◽

Ectopic Expression ◽

Nucleus Pulposus Cell ◽

Intervertebral Disk ◽

Nucleus Pulposus Cells ◽

Disk Degeneration ◽

Direct Target Gene

Aberrant nucleus pulposus cell proliferation is implicated in the development of intervertebral disk degeneration (IDD). Recent studies have suggested that long noncoding RNAs (lncRNAs) can modulate cell proliferation in several pathological conditions. Here, we indicate that expression of SNHG1 was upregulated in IDD tissues compared with control tissues and that higher SNHG1 expression was associated with disk degeneration grade. In addition, we show that ectopic expression of SNHG1 promoted nucleus pulposus (NP) cell proliferation and increased the PCNA and cyclin D1 expression in NP cells. Ectopic expression of SNHG1 inhibited miR-326 expression in nucleus pulposus cells and promoted CCND1 expression, which is a direct target gene of SNHG1. Moreover, we demonstrate that expression of miR-326 was downregulated in IDD tissues compared with control tissues and that lower SNHG1 expression was associated with disk degeneration grade. Expression of miR-326 was negatively associated with SNHG1 expression in disk degeneration tissues. Overexpression of miR-326 inhibited NP cell growth and inhibited PCNA and cyclin D1 expression in NP cells. Furthermore, we show that overexpression of SNHG1 promoted nucleus pulposus cell proliferation through inhibiting miR-326 expression. These data shed novel light on the role of SNHG1 in the pathogenesis of IDD.

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