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Targeting Bradykinin Signaling Pathway: PLGA/BK Microspheres as a Therapeutic Strategy for Delaying Intervertebral Disc Degeneration

ABSTRACT: Targeting Bradykinin Signaling Pathway: PLGA/BK Microspheres as a Therapeutic Strategy for Delaying Intervertebral Disc Degeneration

PROVIDER: PRJNA1162890 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30730948_1.fastq.gz	Fastqsanger.gz
	SRR30730948_2.fastq.gz	Fastqsanger.gz
	SRR30730949_1.fastq.gz	Fastqsanger.gz
	SRR30730949_2.fastq.gz	Fastqsanger.gz
	SRR30730950_1.fastq.gz	Fastqsanger.gz

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Targeting Bradykinin Signaling Pathway: PLGA/BK Microspheres as a Therapeutic Strategy for Delaying Intervertebral Disc Degeneration

Project description:Intervertebral disc degeneration(IVDD) is a common spinal condition with limited effective treatments available. This study aims to investigate the impact of poly(lactic-co-glycolic acid)/Bradykinin (PLGA/BK) microspheres on IVDD and its underlying mechanisms. We collected nucleus pulposus samples from both healthy and degenerated human intervertebral discs and conducted immunohistochemical analyses, revealing reduced BK expression in degenerated tissues. Subsequently, we used BK to treat nucleus pulposus cells and conducted Bulk RNA sequencing (RNA-seq), identifying BK's involvement in cellular senescence, extracellular matrix metabolism, and the PI3K signaling pathway. Further experiments using tert-butyl hydroperoxide (TBHP)-induced cell senescence showed that BK treatment reduced senescence, enhanced extracellular matrix synthesis, and inhibited degradation, along with activation of the PI3K pathway. These effects were mediated through B2R (BK receptor 2) and the downstream PI3K pathway. Following this, we developed sustained-release BK microspheres with an optimized manufacturing process. In vitro co-culture experiments showed no observable toxicity. We established an IVDD model in rat tail vertebrae through fine needle puncture, administering local injections of BK sustained-release microspheres. Using various experimental methods, including X-ray, MRI, histopathology, and immunohistochemistry, we found that these microspheres could slow the progression of IVDD. This study highlights the potential of injectable PLGA/BK microspheres to regulate cellular senescence and extracellular matrix metabolism via the B2R and PI3K pathways, ultimately delaying IVDD.

2024-09-21 | GSE277600 | GEO

PLGA/BK microspheres targeting the bradykinin signaling pathway as a therapeutic strategy to delay intervertebral disc degeneration.

Project description: Not available

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Engineered Senescence-Targeting Apoptotic Extracellular Vesicles-Laden Injectable Hydrogel Microspheres Mitigating Nucleus Pulposus Cell Ferroptosis against Intervertebral Disc Degeneration

Project description:As the rapid growth of aging population, intervertebral disc degeneration (IVDD) becomes a prevalent degenerative disorder in clinical practice. Ferroptosis-induced senescence in nucleus pulposus cells (NPCs) represents a primary pathological mechanism underlying IVDD. Strategies for reducing ferroptosis to delay NPC senescence hold prospects for therapeutic advances. According to previously reported proteomic profiles of ApoEVs, we noticed that most key ferroptosis-regulating proteins were identified in the ApoEVs proteome, including a marked upregulation of GPX4. In this study, we developed injectable hydrogel microspheres integrating with senescent NPC-targeting apoptotic extracellular vesicles (ApoEVs) as GPX4 delivery vehicle and anti-inflammatory diclofenac sodium (DFS) for IVDD treatment. The effect of ApoEVs on reducing NPC ferroptosis and reversing NPC senescence-related metabolic dysfunction and damage was reinforced through modification of reactive oxygen species responsive and senescent NPC-targeting peptide. In vivo experiments and single cell RNA sequencing analysis elucidated that the senescence-targeted system significantly inhibited ferroptosis and inflammatory pathways, and preventedthe transformation of inflammatory NPC phenotypes, thereby offering opportunitiesfor rescuing senescent NPCs from ferroptosis and mitigating IVDD progression.

2026-05-01 | GSE312472 | GEO

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Engineered Senescence-Targeting Apoptotic Extracellular Vesicles-Laden Injectable Hydrogel Microspheres Mitigating Nucleus Pulposus Cell Ferroptosis against Intervertebral Disc Degeneration

Project description:Engineered Senescence-Targeting Apoptotic Extracellular Vesicles-Laden Injectable Hydrogel Microspheres Mitigating Nucleus Pulposus Cell Ferroptosis against Intervertebral Disc Degeneration

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Neonatal and Adult Human Intervertebral Disc scRNA-seq

Project description:We report the single-cell RNA-seq (scRNA-seq) data for human neonatal and adult human intervertebral disc (IVD) scRNA-seq. We sequenced cells harvested from three IVDs of a neonatal baby and one IVD from an adult cadaver.

2021-12-07 | GSE189916 | GEO

Adam8Mutant vs DBA intervertebral disc injury

Project description:Adam8Mutant vs DBA intervertebral disc injury

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Devosia sp. BK strain:BK

Project description:Devosia sp. BK strain:BK Genome sequencing and assembly

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