Related Experiment Video

Updated: Jun 18, 2026

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

Characterization of Wnt/beta-catenin signalling in osteoclasts in multiple myeloma

Ya-Wei Qiang1, Yu Chen, Nathan Brown

  • 1Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, 72205, USA. yqiang@uams.edu <yqiang@uams.edu>

British Journal of Haematology
|December 8, 2009
PubMed

Insights

Wnt/beta-catenin signaling actively suppresses osteoclast formation in multiple myeloma (MM) bone marrow. This pathway in osteoclasts negatively regulates osteoclastogenesis, particularly in an osteoblast-dependent manner.

Area of Science:

  • Bone Biology
  • Cancer Biology
  • Cell Signaling

Background:

  • Wnt/beta-catenin signaling's role in multiple myeloma (MM) bone marrow microenvironment is known to suppress osteoclastogenesis.
  • The precise mechanism, whether direct in osteoclasts or indirect via osteoblasts, requires further elucidation.

Purpose of the Study:

  • To investigate the presence and function of Wnt/beta-catenin signaling specifically within osteoclasts in the context of MM.
  • To determine if Wnt/beta-catenin signaling in osteoclasts directly influences osteoclastogenesis.

Main Methods:

  • Systematic analysis of WNT, FZD, LRP, and TCF gene families in human osteoclasts from MM patients.
  • Assessment of functional Wnt/beta-catenin signaling via beta-catenin accumulation and Dvl-3 protein levels.
  • Evaluation of Wnt antagonist effects (Dkk1, sFRP1) and TCF/LEF transcriptional activity.
  • Analysis of osteoclast formation using conditioned media from osteoblast clones with altered beta-catenin expression.

Main Results:

  • Multiple Wnt signaling components are expressed in human MM osteoclasts.
  • Wnt3a or LiCl treatment induced functional Wnt/beta-catenin signaling, evidenced by beta-catenin and Dvl-3 accumulation, which was inhibited by Wnt antagonists.
  • TCF/LEF transcriptional activity confirmed active canonical Wnt signaling in osteoclasts.
  • Osteoblast supernatants with dominant-negative beta-catenin significantly altered osteoclast formation from MM-derived osteoclasts.

Conclusions:

  • Canonical Wnt/beta-catenin signaling is active in human osteoclasts from MM patients.
  • This signaling pathway in osteoclasts acts as a negative regulator of osteoclastogenesis in the MM bone marrow microenvironment.
  • The regulation appears to be osteoblast-dependent, highlighting a complex interplay in MM bone disease.

More Related Videos

Osteoclast Derivation from Mouse Bone Marrow06:17

Osteoclast Derivation from Mouse Bone Marrow

Published on: November 6, 2014

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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 bone...
Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...