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International journal of molecular sciences2024; 25(23); 12486; doi: 10.3390/ijms252312486

Effect of Low-Molecular-Weight Hyaluronate-Based Nanoparticles on the In Vitro Expression of Cartilage Markers.

Abstract: Hyaluronic acid (HA) is a key component of synovial fluid as it plays a crucial role in joint physiology. Its biological activity is influenced by molecular weight, local concentration, and persistence in joints. High-molecular-weight HA has a consolidated history of clinical use, whereas little is known about the metabolic effect of low-molecular-weight hyaluronate on cartilage differentiation. This study explores the potential of HA-based nanoparticles (NPs) on chondrocytes differentiation in vitro. Starting from 25 kDa and 250 kDa sodium hyaluronate solutions, two types of NPs were prepared by antisolvent precipitation in ethanol. The resulting NPs were dried in the presence of dipalmitoyl phosphatidylcholine, a natural synovial fluid component, then applied on an in vitro model of horse articular chondrocytes: no toxicity was observed and NPs prepared from 250 kDa HA promoted chondrocyte differentiation to a larger extent with respect to corresponding HA solutions, as evidenced by increased gene expression of chondrogenic markers ( and ) and reduced expression of dedifferentiation markers ( and ). These findings suggest that HA-based NPs are more effective at promoting the cellular internalization of the molecule and the differentiation of chondrocytes in vitro and could be a promising platform for drug delivery and cartilage repair.
Publication Date: 2024-11-21 PubMed ID: 39684203PubMed Central: PMC11641601DOI: 10.3390/ijms252312486Google Scholar: Lookup
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  • Journal Article

Summary

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This study investigates the influence of hyaluronic acid (HA)-based nanoparticles, especially of low molecular weight, on the differentiation of chondrocytes (cartilage cells) in laboratory conditions. Findings suggest that these nanoparticles may not only enhance the molecular absorption and differentiation of cartilage cells but could potentially offer a promising tool for drug delivery and cartilage repair.

Background and Objectives

  • The research revolves around hyaluronic acid (HA), a significant constituent of synovial fluid, playing a pivotal role in joint physiology. Its biological activity is contingent upon molecular weight, localized concentration, and durability within the joints.
  • While there is ample knowledge about the clinical use of high-molecular-weight HA, little is known regarding the metabolic influences of low-molecular-weight hyaluronate on cartilage differentiation.
  • This study targets to examine the likely impact of HA-based nanoparticles on chondrocytes differentiation under in vitro conditions.

Research Methodology

  • The researchers prepared two types of nanoparticles from 25 kDa and 250 kDa sodium hyaluronate solutions, using antisolvent precipitation in ethanol.
  • The resultant nanoparticles were dried in the company of dipalmitoyl phosphatidylcholine, a naturally occuring component of synovial fluid.
  • The nanoparticles were then administered on an in vitro model of horse articular chondrocytes. No toxicity was noted during this process.

Key Findings

  • The nanoparticles crafted from 250 kDa HA significantly promoted chondrocyte differentiation rather than the corresponding HA solutions.
  • The increased differentiation was evidenced by the enhanced gene expression of chondrogenic markers while there was a reduced expression of dedifferentiation markers.
  • This finding consequences in stating that HA-based nanoparticles are more efficient in promoting cellular absorption of the molecule and the differentiation of chondrocytes in vitro.

Conclusions and Future Implications

  • The study concludes that HA-based nanoparticles might be highly effective at promoting chondrocyte differentiation and could provide a novel platform for drug delivery and cartilage repair.
  • However, as this study conducted under in vitro conditions, there needs to be further research on the application and implications of using HA-based nanoparticles in a real-world clinical setting.

Cite This Article

APA
Bianchera A, Borghetti P, Ravanetti F, Bertocchi L, De Angelis E, Bettini R. (2024). Effect of Low-Molecular-Weight Hyaluronate-Based Nanoparticles on the In Vitro Expression of Cartilage Markers. Int J Mol Sci, 25(23), 12486. https://doi.org/10.3390/ijms252312486

Publication

ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 25
Issue: 23
PII: 12486

Researcher Affiliations

Bianchera, Annalisa
  • Food and Drug Department, University of Parma, Parco Area Delle Scienze 27/a, 43124 Parma, Italy.
Borghetti, Paolo
  • Department of Veterinary Science, University of Parma, 43124 Parma, Italy.
Ravanetti, Francesca
  • Department of Veterinary Science, University of Parma, 43124 Parma, Italy.
Bertocchi, Laura
  • Food and Drug Department, University of Parma, Parco Area Delle Scienze 27/a, 43124 Parma, Italy.
De Angelis, Elena
  • Department of Veterinary Science, University of Parma, 43124 Parma, Italy.
Bettini, Ruggero
  • Food and Drug Department, University of Parma, Parco Area Delle Scienze 27/a, 43124 Parma, Italy.

MeSH Terms

  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacology
  • Hyaluronic Acid / metabolism
  • Animals
  • Chondrocytes / metabolism
  • Chondrocytes / drug effects
  • Chondrocytes / cytology
  • Nanoparticles / chemistry
  • Molecular Weight
  • Horses
  • Cell Differentiation / drug effects
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / drug effects
  • Chondrogenesis / drug effects
  • Biomarkers / metabolism
  • Cells, Cultured
  • Gene Expression Regulation / drug effects

Grant Funding

  • Glymed PG/2023/299096 Bando Laboratori 2023 (DGR 2097/2022) / Regione Emilia-Romagna

Conflict of Interest Statement

The authors declare no conflicts of interest.

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