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Updated: Jul 5, 2026
08:01
Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Notch inhibits osteoblast differentiation and causes osteopenia
Stefano Zanotti1, Anna Smerdel-Ramoya, Lisa Stadmeyer
1Department of Research, Saint Francis Hospital and Medical Center, 114 Woodland Street, Hartford, Connecticut 06105-1299, USA.
Endocrinology
|April 19, 2008
Summary
Notch signaling in osteoblasts leads to osteopenia by impairing bone formation. Overexpression of Notch intracellular domain (NICD) reduces bone volume and inhibits osteoblastogenesis via Wnt/beta-catenin pathway disruption.
Area of Science:
- Cell Biology
- Skeletal Biology
- Developmental Biology
Background:
- Notch receptors are crucial for cell fate determination.
- The role of Notch signaling in the adult skeleton requires further elucidation.
- Understanding Notch's skeletal function is key to addressing bone diseases.
Purpose of the Study:
- To investigate the impact of Notch signaling on adult bone homeostasis.
- To define the specific mechanisms by which Notch affects osteoblast and osteoclast function.
- To explore the therapeutic potential of modulating Notch signaling in skeletal disorders.
Main Methods:
- Generation of transgenic mice overexpressing Notch intracellular domain (NICD) under the type I collagen promoter.
- In vitro studies using osteoblasts and stromal cells with induced NICD expression via adenoviral Cre recombinase.
- Generation of conditional null notch1 mice and assessment of skeletal phenotypes.
Main Results:
- NICD overexpression in transgenic mice resulted in osteopenia, reduced bone volume, and decreased osteoblast and osteoclast numbers.
- In vitro, NICD impaired osteoblastogenesis and inhibited Wnt/beta-catenin signaling.
- Conditional notch1 deletion showed minimal skeletal effects, suggesting potential redundancy with Notch2, but revealed modest increases in osteoclast activity in females.
Conclusions:
- Notch signaling in osteoblasts directly contributes to osteopenia.
- Impaired osteoblastogenesis and inhibition of Wnt/beta-catenin signaling are key mechanisms.
- Modulating Notch signaling presents a potential therapeutic avenue for bone diseases.
Related Concept Videos
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:29Bone Disorders
Aging and its effect on bone remodeling is the most common cause of bone disorders. In young and healthy people, bone deposition and resorption happen at an equal rate to maintain optimal bone health.
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
01:12Role 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...
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...
01:31Osteoclasts 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...
01:17Hormones and Bone Tissue
The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...