Related Experiment Video
Updated: Dec 5, 2025
08:01
Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
8.2K
Osteoclast differentiation by RANKL and OPG signaling pathways
Nobuyuki Udagawa1,2, Masanori Koide3, Midori Nakamura4,3
1Department of Biochemistry, Matsumoto Dental University, 1780 Gobara, Hiro-oka, Shiojiri, Nagano, 399-0781, Japan. nobuyuki.udagawa@mdu.ac.jp.
Journal of Bone and Mineral Metabolism
|October 20, 2020
Summary
Osteoprotegerin (OPG) and sclerostin are crucial for maintaining bone mass. Novel treatments targeting the RANK-RANKL-OPG system, like anti-Siglec-15 antibodies, show promise in regulating bone remodeling and treating bone loss.
Area of Science:
- Bone Biology
- Cell Signaling
- Biochemistry
Background:
- Bone remodeling involves a balance between osteoclast-mediated resorption and osteoblast-mediated formation.
- Osteoclasts resorb bone, while osteoblasts regulate osteoclastogenesis via receptor activator of nuclear factor-kappa B ligand (RANKL).
- Osteoprotegerin (OPG) inhibits RANKL, preventing osteoclast formation and bone resorption.
Purpose of the Study:
- To review experimental findings on signal transduction pathways regulating RANKL and OPG expression.
- To elucidate the roles of OPG, sclerostin, and novel therapeutic targets in bone homeostasis.
Main Methods:
- Utilized OPG gene-deficient mice to assess bone maintenance roles.
- Investigated the effects of leukemia inhibitory factor (LIF) on sclerostin expression.
- Examined the impact of WP9QY peptide and anti-sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) antibody on osteoclast and osteoblast activity in vitro.
Main Results:
- OPG and sclerostin are vital for cortical and alveolar bone maintenance.
- Osteoclast-derived LIF decreases sclerostin and promotes bone formation.
- WP9QY peptide inhibited osteoclast differentiation and stimulated osteoblast proliferation.
- Anti-Siglec-15 antibody suppressed osteoclast formation and activity while promoting osteoblast appearance.
Conclusions:
- Bone mass is regulated by the RANK-RANKL-OPG system, controlling osteoclast differentiation, activation, and survival.
- Targeting pathways involving OPG, sclerostin, and Siglec-15 offers potential therapeutic strategies for bone disorders.
More Related Videos
Related Concept Videos
01:31Osteoclasts in Bone Remodeling
3.6K
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...
3.6K
01:15Differentiation of Common Myeloid Progenitor Cells
3.7K
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
3.7K
01:16TGF - β Signaling Pathway
9.8K
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...
9.8K
03:14Notch Signaling Pathway
5.9K
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...
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...
5.9K
01:30Bone Cells and Tissue
7.5K
Bones contain a relatively small number of cells entrenched in a matrix of organic and inorganic components. Although bone cells compose only a small amount of the bone volume, they are crucial to its function. Four types of cells are found within the bone tissue— osteoblasts, osteocytes, osteogenic cells, and osteoclasts.
Osteoblasts and Osteocytes
The osteoblast is the bone cell responsible for forming new bone tissue. It is found in the growing portions of bone, including the...
Osteoblasts and Osteocytes
The osteoblast is the bone cell responsible for forming new bone tissue. It is found in the growing portions of bone, including the...
7.5K
01:28Role of Hematopoietic Growth Factors
2.7K
Hematopoietic growth factors are molecules that regulate the differentiation rate of hematopoietic stem cells (HSCs). Erythropoietin (EPO), primarily produced by the kidneys, plays a crucial role in erythrocyte production. When oxygen levels in the blood are low, EPO is released into the bloodstream, reaching the bone marrow, where it stimulates HSCs to differentiate and mature into erythrocytes, which are vital for oxygen transport.
Thrombopoietin (TPO), mainly released by the liver,...
Thrombopoietin (TPO), mainly released by the liver,...
2.7K