Related Experiment Video

Updated: Jun 26, 2026

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
08:01

Stimulation of Notch Signaling in Mouse Osteoclast Precursors

Published on: February 28, 2017

Glucocorticoid-dependent Wnt signaling by mature osteoblasts is a key regulator of cranial skeletal development in

Hong Zhou1, Wendy Mak, Robert Kalak

  • 1Bone Research Program, ANZAC Research Institute, The University of Sydney, Sydney, NSW 2139, Australia. hzhou@med.usyd.edu.au

Development (Cambridge, England)
|January 15, 2009
PubMed

Insights

Glucocorticoids regulate cranial skeleton development by controlling osteoblast differentiation and cartilage removal. Disrupting this signaling in mice led to cranial bone defects and impaired Wnt signaling pathways.

Area of Science:

  • Endocrinology
  • Developmental Biology
  • Skeletal Biology

Background:

  • Glucocorticoids influence bone cell differentiation and mesenchymal stem cell fate.
  • Osteoblasts play a crucial role in regulating skeletal development.

Purpose of the Study:

  • To investigate the molecular mechanisms by which glucocorticoids regulate cranial skeleton development.
  • To identify the role of osteoblast-specific glucocorticoid signaling in intramembranous bone formation.

Main Methods:

  • Utilized cell-specific transgenic mice with disrupted intracellular glucocorticoid signaling in osteoblasts.
  • Analyzed cranial skeleton phenotypes in embryonic and neonatal transgenic mice.
  • Assessed gene expression of key developmental regulators (Mmp14, Wnt9a, Wnt10b) and beta-catenin accumulation.
  • Administered Wnt3a protein to evaluate rescue effects.

Main Results:

  • Transgenic mice exhibited cranial hypoplasia, osteopenia, disorganized cranial bones, and increased suture patency.
  • Ectopic cartilage differentiation and impaired postnatal cartilage removal were observed in the sagittal and parietal sutures.
  • Reduced expression of Mmp14, Wnt9a, and Wnt10b, along with decreased beta-catenin accumulation, was noted in transgenic animals.
  • Supracalvarial Wnt3a injection rescued the cranial phenotype.

Conclusions:

  • Glucocorticoids, acting primarily through mature osteoblasts, regulate cranial skeleton development via a novel molecular pathway.
  • Osteoblasts orchestrate intramembranous bone formation by directing mesenchymal cell differentiation and controlling cartilage dissolution.
  • The glucocorticoid-Wnt-Mmp14 axis is critical for proper cranial bone development and postnatal cartilage remodeling.

More Related Videos

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model08:42

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model

Published on: July 3, 2020

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...
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...
Bone Formation by Endochondral Ossification01:24

Bone Formation by Endochondral Ossification

Bone formation, or ossification, begins around the sixth to seventh week of embryonic development. Most bones develop from a cartilaginous template through the process of endochondral ossification. Cartilage formation begins when clusters of mesenchymal cells differentiate into chondrocytes. These chondrocytes proliferate rapidly and secrete an extracellular matrix that becomes encased in a membrane called the perichondrium. The resulting cartilage model provides a template that resembles the...
Bone Remodeling01:40

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
Bone Formation by Intramembranous Ossification01:29

Bone Formation by Intramembranous Ossification

Intramembranous ossification is one of the two processes involved in the development of bones within an embryo. The flat bones of the face, most of the cranial bones, and the clavicles are formed via this process. During intramembranous ossification, the bones develop directly from sheets of undifferentiated mesenchymal connective tissue.
The process begins when mesenchymal cells in the embryonic skeleton gather together and differentiate into osteogenic cells, which then develop into...