D-chiro-inositol negatively regulates the formation of multinucleated osteoclasts by down-regulating NFATc1

Jungeun Yu1, Seunga Choi, Eui-Soon Park

  • 1Department of Microbiology and Molecular Biology, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon, 305-764, Republic of Korea.

Abstract

Insights

D-chiro-inositol inhibits osteoclast formation by reducing cell fusion and down-regulating NFATc1 expression. This suggests D-chiro-inositol may treat inflammatory bone loss and osteoporosis.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Bone Metabolism

Background:

  • Osteoclasts (OCs) are critical for bone resorption; their accelerated activity contributes to diseases like osteoporosis.
  • D-pinitol is converted to D-chiro-inositol, a potential insulin-like mediator.
  • Understanding D-chiro-inositol's role in OC differentiation is crucial for bone health.

Purpose of the Study:

  • To investigate the effect of D-chiro-inositol on osteoclast differentiation.
  • To determine if D-chiro-inositol influences osteoclast formation and gene expression.

Main Methods:

  • Osteoclastogenesis cultures were used with tartrate-resistant acid phosphatase (TRAP) staining.
  • Cell fusion assays were performed with purified OC precursors.
  • The impact of D-chiro-inositol on nuclear factor of activated T cells c1 (NFATc1) and OC marker gene expression was analyzed.

Main Results:

  • D-chiro-inositol inhibited receptor activator of NF-κB ligand-induced OC differentiation.
  • Multinucleated OC formation via cell-cell fusion was dose-dependently reduced by D-chiro-inositol.
  • D-chiro-inositol suppressed osteoclastogenic gene expression by down-regulating NFATc1.

Conclusions:

  • D-chiro-inositol negatively regulates osteoclastogenesis by inhibiting multinucleated OC formation.
  • Down-regulation of NFATc1 by D-chiro-inositol leads to reduced OC marker gene expression.
  • D-chiro-inositol shows potential as a therapeutic agent for inflammatory bone diseases and diabetic osteoporosis.

Related Concept Videos

Chromatin Immunoprecipitation- ChIP02:36

Chromatin Immunoprecipitation- ChIP

Chromatin immunoprecipitation, or ChIP, is an antibody-based technique used to identify sites on DNA that bind to transcription factors of interest or histone proteins. It also helps determine the type of histone modifications such as acetylation, phosphorylation, or methylation.
Types of ChIP
ChIP can be divided into two types - X-ChIP and N-ChIP. X-ChIP involves in vivo cross-linking of histones and regulatory proteins to DNA, fragmenting the DNA by sonication, and isolating the protein-DNA...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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 heterodimer of NF-κB...
Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
X-Inactivation01:58

X-Inactivation

The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.