MicroRNA-200c Attenuates Periodontitis by Modulating Proinflammatory and Osteoclastogenic Mediators

Adil Akkouch1, Min Zhu1, Miguel Romero-Bustillos2

  • 11Iowa Institute for Oral Health Research, College of Dentistry, The University of Iowa, Iowa City, Iowa.

Insights

MicroRNA-200c reduces inflammation and bone loss in periodontitis. This study shows miR-200c protects against alveolar bone resorption and inflammatory mediators in both cell and animal models.

Area of Science:

  • Periodontology
  • Molecular Biology
  • Biomedical Engineering

Background:

  • Periodontitis involves inflammation and alveolar bone resorption.
  • MicroRNAs (miRNAs) play roles in regulating inflammatory and bone remodeling processes.
  • miR-200c's potential therapeutic role in periodontitis requires investigation.

Purpose of the Study:

  • To investigate the therapeutic potential of microRNA (miR)-200c in attenuating inflammation and alveolar bone resorption in periodontitis.
  • To evaluate the effects of miR-200c overexpression on inflammatory and osteoclastogenic mediators in human gingival fibroblasts (HGFs) challenged with Porphyromonas gingivalis lipopolysaccharide (LPS-PG).
  • To assess the efficacy of local miR-200c delivery in a rat model of periodontitis.

Main Methods:

  • In vitro study using primary HGFs transfected with miR-200c using polyethylenimine (PEI).
  • In vivo study using a rat model of periodontitis induced by LPS injection.
  • Local delivery of miR-200c via PEI-plasmid nanoplexes.
  • Analysis of inflammatory mediators (IL-6, IL-8, IFRD1, p65, p50), osteoclastogenic factors (RANKL/OPG ratio), micro-computed tomography, and histomorphometry.

Main Results:

  • Overexpression of miR-200c in HGFs reduced IL-6, IL-8, IFRD1, p65, and p50 expression following LPS-PG challenge.
  • Local injection of miR-200c in rats significantly upregulated gingival miR-200c expression.
  • miR-200c treatment reduced IL-6, IL-8, IFRD1, and the RANKL/OPG ratio, and effectively protected against alveolar bone resorption in the rat model.

Conclusions:

  • miR-200c effectively suppresses inflammatory and osteoclastogenic mediators in periodontitis.
  • Local delivery of miR-200c demonstrates therapeutic potential in preventing periodontitis-associated alveolar bone loss.
  • miR-200c represents a promising therapeutic agent for periodontitis management.

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
24.1K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.9K
Transcription Attenuation in Prokaryotes02:42

Transcription Attenuation in Prokaryotes

Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure.  Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
18.2K
Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein01:20

Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein

Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
854
Receptor-mediated Endocytosis01:39

Receptor-mediated Endocytosis

Overview
110.7K
Receptor-mediated Endocytosis01:20

Receptor-mediated Endocytosis

Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
7.6K