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Related Concept Videos

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...
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
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Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
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Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
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Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...

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Related Experiment Video

Updated: Jun 21, 2026

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
09:37

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

Published on: March 15, 2018

Nrf2 dynamically regulates RANKL-induced osteoclastogenesis and cathepsin K function.

Cesar A Speck-Hernandez1, Taíssa C de Souza Furtado2, Laisa Y de Souza3

  • 1Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil; Laboratory of Bone Biology, Department of Biomolecular Sciences, School of Pharmaceutical Sciences, Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.

The Journal of Biological Chemistry
|June 19, 2026
PubMed
Summary
This summary is machine-generated.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is crucial for osteoclast function. It balances reactive oxygen species (ROS) and maintains lysosomal integrity, impacting bone resorption and Cathepsin K activity.

Keywords:
Lipid PeroxidationMitochondriaNrf2OsteoclastsOxidative StressROS

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Last Updated: Jun 21, 2026

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
09:37

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

Published on: March 15, 2018

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

Area of Science:

  • Cell Biology
  • Biochemistry
  • Immunology

Background:

  • Osteoclasts resorb bone via Cathepsin K.
  • RANKL signaling drives osteoclastogenesis and reactive oxygen species (ROS) production.
  • Excessive ROS causes cellular damage, countered by antioxidant defenses like the Nrf2 pathway.

Purpose of the Study:

  • To investigate the dynamic regulation of antioxidant responses during osteoclastogenesis and activation.
  • To elucidate the dual role of RANKL in modulating antioxidant defenses in osteoclasts.
  • To determine the specific functions of Nrf2 in osteoclast differentiation and resorptive activity.

Main Methods:

  • Bioinformatic analysis.
  • Genetic manipulation using engineered mouse models.
  • In vitro studies of Nrf2-deficient osteoclasts.

Main Results:

  • RANKL differentially regulates antioxidant responses, suppressing glutathione defenses while activating Nrf2.
  • Nrf2 deficiency enhances osteoclast formation but impairs resorptive function and Cathepsin K activity.
  • Nrf2-deficient osteoclasts show increased lipid peroxidation, mitochondrial dysfunction, and lysosomal instability.

Conclusions:

  • Nrf2 is a critical regulator of osteoclast function, essential for redox balance and lysosomal integrity.
  • Nrf2 plays a key role in maintaining osteoclast resorptive capacity.
  • This study highlights the intricate interplay between RANKL-induced oxidative signaling and Nrf2-mediated antioxidant regulation in bone resorption.