In vitro and ex vivo screening of microRNA combinations with enhanced cell penetrating peptides to stimulate intervertebral disc regeneration DOI Creative Commons

Tara Ní Néill,

Marcos N. Barcellona,

Niamh Wilson

et al.

JOR Spine, Journal Year: 2024, Volume and Issue: 7(4)

Published: Dec. 1, 2024

Abstract Background Low back pain (LBP) is predominantly caused by degeneration of the intervertebral disc (IVD) and central nucleus pulposus (NP) region. Conservative treatments fail to restore function, motivating exploration nucleic acid therapies, such as use microRNAs (miRNAs). miRNAs have potential modulate expression discogenic factors, while silencing catabolic cascade associated with degeneration. To deliver these miRNAs, nonviral cell penetrating peptides (CPPs) are gaining favor given their low immunogenicity strong targeting ability. Single miRNA therapies been investigated for IVD repair, however dual delivery strategies not commonly examined may augment regeneration. Materials methods Transfection four pro‐discogenic (miRNA mimics:140‐5p; 149‐5p inhibitors: 141‐3p; 221‐3p) six pairings was performed using two CPPs, RALA GET peptide (FLR), in primary rat NP monolayer culture, an ex vivo organ culture model caudal discs. Protein (aggrecan, collagen type II, SOX9) markers (ADAMTS5 MMP13) were assessed. Results Monolayer investigations signified enhanced marker following delivery, signifying a synergistic effect when compared single transfection. Utilization appropriate emphasized our experiment, revealing establishment regenerative microenvironment characterized reduced enzyme activity matrix deposition, particularly concurrent FLR‐miRNA‐149‐5p mimic miRNA‐221‐3p inhibitor. Bioinformatics analysis miRNA‐149‐5p inhibitor identified distinct targets, pathways, interactions, suggesting mode action this amplified response. Conclusion Our findings suggest + create anti‐catabolic niche within foster regeneration moderate cases degeneration, which could be utilized further studies overarching aim developing LBP.

Language: Английский

Microenvironment-responsive metal-phenolic network release platform with ROS scavenging, anti-pyroptosis, and ECM regeneration for intervertebral disc degeneration DOI Creative Commons
Hao Zhou, Jinpeng He, Renfeng Liu

et al.

Bioactive Materials, Journal Year: 2024, Volume and Issue: 37, P. 51 - 71

Published: March 15, 2024

Intervertebral disc degeneration (IVDD) can be caused by aging, injury, and genetic factors. The pathological changes associated with IVDD include the excessive accumulation of reactive oxygen species (ROS), cellular pyroptosis, extracellular matrix (ECM) degradation. There are currently no approved specific molecular therapies for IVDD. In this study, we developed a multifunctional microenvironment-responsive metal-phenolic network release platform, termed TMP@Alg-PBA/PVA, which could treat (IL-1β)-induced (TA-Mn-PVP, TMP) released from platform targeted mitochondria to efficiently scavenge ROS reduce ECM Pyroptosis was suppressed through inhibition IL-17/ERK signaling pathway. These findings demonstrate versatility platform. And in rat model IVDD, TMP@Alg-PBA/PVA exhibited excellent therapeutic effects reducing progression disease. therefore, presents clinical potential treatment

Language: Английский

Citations

22
Mitochondrial dysfunction: a new molecular mechanism of intervertebral disc degeneration DOI
Chao Song, Yulin Xu, Qinghua Peng

et al.

Inflammation Research, Journal Year: 2023, Volume and Issue: 72(12), P. 2249 - 2260

Published: Nov. 5, 2023

Language: Английский

Citations

26
The Sanbi Decoction alleviates intervertebral disc degeneration in rats through intestinal flora and serum metabolic homeostasis modulation DOI
Nan Wang, Shuang Chen,

Yimin Xie

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 127, P. 155480 - 155480

Published: Feb. 24, 2024

Language: Английский

Citations

8
The role of pyroptosis in metabolism and metabolic disease DOI Open Access

Zhuyuan Zheng,

Shaojie Yang,

Wanlin Dai

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116863 - 116863

Published: June 7, 2024

Pyroptosis is a lytic and pro-inflammatory form of regulated cell death characterized by the formation membrane pores mediated gasdermin protein family. Two main activation pathways have been documented: caspase-1-dependent canonical pathway caspase-4/5/11-dependent noncanonical pathway. leads to swelling, lysis, subsequent release inflammatory mediators, including interleukin-1β (IL-1β) interleukin-18 (IL-18). Chronic inflammation well-established foundation driver for development metabolic diseases. Conversely, dysregulation can also induce cellular pyroptosis. Recent studies highlighted significant role pyroptosis modulation in various diseases, type 2 diabetes mellitus, obesity, (dysfunction) associated fatty liver disease. These findings suggest that may serve as promising novel therapeutic target This paper reviews an in-depth study current advancements understanding progression

Language: Английский

Citations

7
Single‐Cell Analysis Integrated With Machine Learning Elucidates the Mechanisms of Nucleus Pulposus Cells Apoptosis in Intervertebral Disc Degeneration and Therapeutic Interventions DOI Creative Commons
Chao Song, Xiaofei Wu, Chaoqi Chen

et al.

JOR Spine, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 20, 2025

ABSTRACT Background The molecular of intervertebral disc degeneration (IVDD) is still unclear. When it comes to treating decoction, traditional Chinese medicine effective. In particular, the Duhuo (Radix Angelicae Biseratae) may be particularly helpful. Purpose To identify nucleus pulposus cells (NPCs) subpopulations and immune clarify mechanism IVDD therapy, offering recommendations for diagnosis treatment. Methods targets from Genecards microarray data biological databases. find key genes pathways underlying IVDD, multiple machine learning techniques were used. associated with NPCs as revealed by single‐cell analysis, immunological infiltration was identified Immune Cell AI. validate which activity affects network pharmacology docking employed. Results process linked like TP53, JUN, PTEN, IL1B, ERBB2, MAPK8, CASP9, PTK2, etc. main mechanisms involved in this are responses, inflammatory factors expression, cellular responses mechanical stimuli, NPC apoptosis. AI discovered a correlation between CD4 naïve, B cell, monocyte, NK, macrophage development IVDD. subtypes namely fibroNPCs, adhesion NPCs, regulatory homeostatic hypertrophic chondrocyte‐like (HT‐CL NPCs), subject mapping. We also found that Osthole, Columbianadin, Bergapten, principal blood entry components Dohuo, have role modulating PTGS1, PARP1, Conclusion exist HT‐CL NPCs. Furthermore, variety cell infiltrates, monocyte macrophage, significant impact on advancement Duhuo, absorb via controlling death

Language: Английский

Citations

1
5-Azacytidine inhibits endoplasmic reticulum stress and apoptosis of nucleus pulposus cells by preserving PPARγ via promoter demethylation DOI
Peng Cheng, Huan Li, Haiwei Chen

et al.

In Vitro Cellular & Developmental Biology - Animal, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Language: Английский

Citations

1
Preserving the Immune‐Privileged Niche of the Nucleus Pulposus: Safeguarding Intervertebral Discs from Degeneration after Discectomy with Synthetic Mucin Hydrogel Injection DOI Creative Commons
Huan Wang, Song Chen, Zhao Liu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(43)

Published: Aug. 29, 2024

Abstract Intervertebral disc (IVD) herniation is a prevalent spinal disorder, often necessitating surgical intervention such as microdiscectomy for symptomatic relief and nerve decompression. IVDs comprise gel‐like nucleus pulposus (NP) encased by an annulus fibrosus (AF), their avascular nature renders them immune‐privileged. Microdiscectomy exposes the residual NP to immune system, precipitating cell infiltration attack that exacerbates IVD degeneration. While many efforts in tissue engineering field are directed toward regeneration, inherently limited regenerative capacity due low‐cellularity of challenging mechanical environment spine impedes success. This study, aiming prevent degeneration post‐microdiscectomy, utilizes mucin‐derived gels (Muc‐gels) form gel at site, inspired natural mucin coating on living organisms evade reorganization. It shown type I macrophages present severely degenerated human discs. Encapsulating within Muc‐gels prevents fibrous encapsulation macrophage mouse subcutaneous model. The injection rat tail model up 24 weeks post‐operation. Mechanistic investigations indicate attenuate into NPs, offering durable protection against post‐microdiscectomy.

Language: Английский

Citations

6
IL-1β-mediated inflammatory responses in intervertebral disc degeneration: Mechanisms, signaling pathways, and therapeutic potential DOI Creative Commons
Hongtao Li, Hongyu Pan, Changming Xiao

et al.

Heliyon, Journal Year: 2023, Volume and Issue: 9(9), P. e19951 - e19951

Published: Sept. 1, 2023

Intervertebral disc degeneration (IDD) has been widely recognized as the primary cause of low back pain and is one major chronic diseases imposing a severe socioeconomic burden worldwide. IDD degenerative process characterized by inflammatory responses, its underlying pathological mechanisms remain complex. Genetic, developmental, biochemical, biomechanical factors contribute to development IDD. There pressing need for an effective non-surgical treatment, mainly due lack comprehensive understanding specific involved therapeutic targets Recently, interleukin (IL)-1β essential factor key mediator in Current studies have found that IL-1β affecting metabolism extracellular matrix regulating cell death (RCD), such apoptosis, pyroptosis, ferroptosis (a new form RCD). Although analysis clinical samples from different laboratories confirmed how induced IDD, signal transduction pathway, role mediated remains unclear. This review describes molecules IL-1β-mediated their roles resolving Understanding signaling pathways may lead class promote remission patients. aims provide framework treatment analyzing mechanism function related IL-1β, especially terms inflammation, metabolism, regulation.

Language: Английский

Citations

11
Risk factors associated with low-grade virulent infection in intervertebral disc degeneration: a systematic review and meta-analysis DOI
Mingtao Zhang,

Jingwen Jia,

Liangna Deng

et al.

The Spine Journal, Journal Year: 2024, Volume and Issue: 24(6), P. 1034 - 1045

Published: Feb. 15, 2024

Language: Английский

Citations

4
Silencing DDX3 Attenuates Interleukin-1β-Induced Intervertebral Disc Degeneration Through Inhibiting Pyroptosis DOI

Hongfa Zhong,

Mingheng Li, Haijian Wu

et al.

Inflammation, Journal Year: 2024, Volume and Issue: unknown

Published: May 13, 2024

Language: Английский

Citations

4