Evidence map›Paper›PMID 36904410›Full record

ArticlePolymers2023

MMP-2 Silencing through siRNA Loaded Positively-Charged Nanoparticles (AcPEI-NPs) Counteracts Chondrocyte De-Differentiation.

Raffaele Conte, Mauro Finicelli, Alessia Borrone, Sabrina Margarucci, Gianfranco Peluso, Anna Calarco, Michela Bosetti

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In one paragraph

Article in Polymers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Raffaele ConteElleva Pharma s.r.l., via P. Castellino 111, 80131 Naples, Italy.ORCID 0000-0002-6266-4991
Mauro FinicelliResearch Institute on Terrestrial Ecosystems (IRET)-CNR, Via P. Castellino 111, 80131 Naples, Italy.ORCID 0000-0003-2289-0916
Alessia BorroneDipartimento di Scienze del Farmaco (DSF), Università Piemonte Orientale "A. Avogadro", Largo Donegani 2, 28100 Novara, Italy.
Sabrina MargarucciResearch Institute on Terrestrial Ecosystems (IRET)-CNR, Via P. Castellino 111, 80131 Naples, Italy.
Gianfranco PelusoResearch Institute on Terrestrial Ecosystems (IRET)-CNR, Via P. Castellino 111, 80131 Naples, Italy.
Anna CalarcoResearch Institute on Terrestrial Ecosystems (IRET)-CNR, Via P. Castellino 111, 80131 Naples, Italy.ORCID 0000-0002-1441-7662
Michela BosettiDipartimento di Scienze del Farmaco (DSF), Università Piemonte Orientale "A. Avogadro", Largo Donegani 2, 28100 Novara, Italy.ORCID 0000-0002-3682-8702

Funding

European Union MSCA-RISE 2016 Project "VAHVISTUS" (Grant 734759)Ministero Istruzione PON 03 PE_00110_1/ptd1_000410Ministry of Education, Universities and Research PRIN 201288JKYYRegione Campania FESR 2014_2020 ABILTECH
6 · The paper itself

Abstract

The abnormal matrix remodeling process, as well as inflammation, angiogenesis, and tumor metastasis, are related to an increase in the synthesis and secretion of matrix metalloproteinases (MMPs), the zinc-dependent proteolytic endopeptidases. Recent studies have evidenced MMPs' role in osteoarthritis (OA) development, during which chondrocytes undergo hypertrophic differentiation and exhibit enhanced catabolism. The trait of OA is extracellular matrix (ECM) progressive degradation regulated by many factors, in which MMPs play an important role, which indicates them as potential therapeutic targets. Herein, a small interfering RNA (siRNA) delivery system able to suppress MMPs' activity was synthetized. Results demonstrated that positively charged nanoparticles (AcPEI-NPs) complexed with MMP-2 siRNA are efficiently internalized by cells with endosomal escape. Moreover, avoiding lysosome degradation, MMP2/AcPEI nanocomplex increases nucleic acid delivery efficiency. Gel zymography, RT-PCR, and ELISA analyses confirmed MMP2/AcPEI nanocomplex activity even when embedded within collagen matrix resembling the natural extracellular matrix. Further, the inhibition of in vitro collagen degradation exerts a protective effect on chondrocyte dedifferentiation. The suppression of MMP-2 activity, preventing matrix degradation, protects chondrocytes against degeneration and supporting ECM homeostasis in articular cartilage. These encouraging results promote further investigation to validate the utilization of MMP-2 siRNA as ''molecular switch'' able to counteract osteoarthritis.

Indexed as

acetylated-PEIchondrocytesde-differentiationMMPsnanoparticlessiRNA

Identifiers

PMID36904410
PMCPMC10007186

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.