Related Experiment Video

Updated: Sep 24, 2025

A Simple Pit Assay Protocol to Visualize and Quantify Osteoclastic Resorption In Vitro
07:03

A Simple Pit Assay Protocol to Visualize and Quantify Osteoclastic Resorption In Vitro

Published on: June 16, 2022

6.5K

IL-10 inhibits osteoclast differentiation and osteolysis through MEG3/IRF8 pathway

Xuren Gao1, Jian Ge1, Wangchen Zhou1

  • 1Department of Orthopedics, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.

Cellular Signalling
|May 7, 2022
PubMed
Abstract

Insights

Long non-coding RNA MEG3 inhibits osteoclast differentiation and wear particle-induced osteolysis by regulating IRF8 expression. Interleukin-10 may exert its effects through the MEG3/IRF8 pathway.

Area of Science:

  • Biomedical Engineering
  • Molecular Biology
  • Immunology

Background:

  • Osteolysis, driven by wear particles, is a primary cause of joint replacement failure.
  • Inhibiting osteoclast differentiation is a key strategy to mitigate wear particle-induced osteolysis.

Purpose of the Study:

  • To investigate the role of long non-coding RNA maternally expressed gene 3 (MEG3) in osteoclast differentiation and wear particle-induced osteolysis.
  • To elucidate the mechanism by which interleukin-10 (IL-10) influences osteoclast differentiation.

Main Methods:

  • Established a polymethylmethacrylate (PMMA)-induced osteolysis mouse model and a receptor activator of nuclear factor-B ligand (RANKL)-induced osteoclast differentiation model.
  • Utilized techniques including TRAP staining, HE staining, immunohistochemistry, bone resorption assays, dual-luciferase assays, RNA pull-down, RNA immunoprecipitation, and chromatin immunoprecipitation.

Main Results:

  • MEG3 levels increased, while interferon regulatory factor 8 (IRF8) levels decreased in PMMA-induced osteolysis.
  • IL-10 inhibited osteoclast differentiation and MEG3 expression, while promoting MEG3 methylation.
  • MEG3 knockdown reduced osteoclast differentiation and osteolysis, an effect weakened by IRF8 knockdown. MEG3 binds STAT1, which in turn binds IRF8, with MEG3 overexpression inhibiting STAT1-IRF8 binding.

Conclusions:

  • MEG3 regulates IRF8 expression via STAT1, impacting osteoclast differentiation and wear particle-induced osteolysis.
  • The IL-10 pathway may inhibit osteoclast differentiation through the MEG3/IRF8 axis.
Keywords:
IL-10IRF8OsteoclastsOsteolysisSTAT1lncRNA MEG3

More Related Videos

Effect of Anti-c-fms Antibody on Osteoclast Formation and Proliferation of Osteoclast Precursor In Vitro07:51

Effect of Anti-c-fms Antibody on Osteoclast Formation and Proliferation of Osteoclast Precursor In Vitro

Published on: March 18, 2019

6.1K
A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation09:37

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

Published on: March 15, 2018

13.3K

Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.4K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.8K
Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
3.2K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.9K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.2K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.4K