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Related Concept Videos

Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

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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...
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Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
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Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
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Inhibition of Cdk Activity02:34

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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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Bone Remodeling01:40

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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.
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Related Experiment Video

Updated: Mar 7, 2026

Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines
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Cabozantinib targets bone microenvironment modulating human osteoclast and osteoblast functions.

Marco Fioramonti1, Daniele Santini1, Michele Iuliani1

  • 1Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy.

Oncotarget
|February 23, 2017
PubMed
Summary

Cabozantinib directly inhibits osteoclast function and bone resorption. It also indirectly reduces bone resorption by altering osteoblast signaling, offering potential benefits for bone health in cancer patients.

Keywords:
bone microenvironmentcabozantinibhuman primary cellsosteoprotegerin (OPG)receptor activator of nuclear factor-kb ligand (RANKL)

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A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders
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A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
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A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders
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Area of Science:

  • Oncology
  • Bone Biology
  • Pharmacology

Background:

  • Cabozantinib is a dual inhibitor of c-MET and VEGFR2, showing efficacy in castration-resistant prostate cancer and metastatic renal carcinoma.
  • The drug's impact on the bone microenvironment, particularly osteoclast and osteoblast function, remains incompletely understood.

Purpose of the Study:

  • To investigate the direct effects of cabozantinib on primary human osteoclasts and osteoblasts.
  • To elucidate the mechanisms by which cabozantinib influences bone remodeling processes.

Main Methods:

  • Osteoclasts were differentiated from human monocytes, and osteoblasts from human mesenchymal stem cells.
  • Assays included tartrate-resistant acid phosphatase (TRAP) staining, bone resorption assays, alkaline phosphatase staining, and alizarin red staining.
  • Gene and protein expression of key markers (TRAP, Cathepsin K, RANK, OPG, RANKL) were analyzed.

Main Results:

  • Cabozantinib significantly inhibited osteoclast differentiation and bone resorption activity at non-cytotoxic doses.
  • The drug down-modulated key osteoclast marker genes: TRAP, Cathepsin K, and RANK.
  • Cabozantinib increased osteoprotegerin (OPG) and decreased Receptor Activator of Nuclear Factor k B Ligand (RANKL) in osteoblasts, reducing the RANKL/OPG ratio.

Conclusions:

  • Cabozantinib exerts direct inhibitory effects on osteoclast differentiation and function.
  • The drug also exhibits indirect anti-resorptive effects by modulating osteoblast OPG and RANKL expression.
  • These findings highlight cabozantinib's potential to favorably impact the bone microenvironment in cancer patients.