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

2019 ◽  
Vol 120 (12) ◽  
pp. 19318-19329 ◽  
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

MiR-532-3p Suppresses Nucleus Pulposus Cells Proliferation and Extracellular Matrix Production, Promotes Cell Apoptosis via Targeting High Mobility Group AT-Hook 2

2021 ◽  
Vol 11 (7) ◽  
pp. 1313-1319
Author(s):  
Zhisheng Long ◽  
Feipeng Gong ◽  
Chen Li
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Nucleus Pulposus ◽  
Cell Apoptosis ◽  
High Mobility ◽  
High Mobility Group ◽  
Luciferase Reporter ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Nucleus Pulposus Cells

The present study aimed to investigate the function and mechanism of microRNA (miR)-532-3p in intervertebral disc degeneration (IDD). Further, whether miR-532-3p regulates HMGA2 in nucleus pulposus (NP) cells was explored. We collected human nucleus pulposus (NP) tissues from the patients with IDD, and detected miR-532-3p in NP tissues using RT-qPCR. MiR-532-3p mimic and inhibitor were constructed, and they were transfected into the human nucleus pulposus cells (HNPCs) by Lipofectamine 3000. MTT assay was conducted to determine cell proliferation. Cell apoptosis and extracellular matrix remodeling were examined by flow cytometric, Caspase 3/8 Assay Kits and Western blot. A dual-luciferase reporter assay was applied to investigate whether miR-532-3p targets High mobility group AT-hook 2 (HMGA2). We found miR-532-3p expression level was significantly increased in NP tissues of IDD patients, comparing with the controls. MiR-532-3p exerted an inhibitory effect on HNPCs proliferation; however, cell apoptosis and the degradation of extracellular matrix were induced by miR-532-3p. MiR-532-3p directly targets HMGA2, and HMGA2 overexpression reversed the role of miR-532-3p mimic in HNPCs proliferation, apoptosis, and extracellular matrix remodeling. Our study is the first to report that miR-532-3p might suppress NP cell proliferation, promote cell apoptosis and inhibit ECM production of NP cells via targeting HMGA2, thus facilitating the progression of IDD. MiR-532-3p was supposed to be a novel target for the treatment of IDD.

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

2018 ◽  
Vol 315 (1) ◽  
pp. C21-C27 ◽  
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.

scholarly journals Raloxifene retards the progression of adjacent segmental intervertebral disc degeneration by inhibiting apoptosis of nucleus pulposus in ovariectomized rats

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Qi Sun ◽  
Xin-Yu Nan ◽  
Fa-Ming Tian ◽  
Fang Liu ◽  
Shao-Hua Ping ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Lumbar Fusion ◽  
B Cell Lymphoma ◽  
Intervertebral Disk ◽  
Ovariectomized Rats ◽  
Tunel Staining ◽  
Mineral Density ◽  
Vertebral Osteoporosis ◽  
Intervertebral Disk Degeneration ◽  
Disk Degeneration

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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