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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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Updated: Jun 12, 2025

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Single-Cell Transcriptomic Analysis Identifies Senescent Osteocytes That Trigger Bone Destruction in Breast Cancer

Japneet Kaur1, Manish Adhikari1, Hayley M Sabol1

  • 1Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

Cancer Research
|September 23, 2024
PubMed
Summary
This summary is machine-generated.

Breast cancer cells cause osteocyte senescence, a process that drives bone destruction in metastases. Targeting these senescent cells with senolytics can reduce bone loss and preserve bone mass in patients.

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Area of Science:

  • Oncology
  • Cell Biology
  • Bone Biology

Background:

  • Breast cancer bone metastases are a significant cause of morbidity, increasing fracture risk and mortality.
  • Tumor cell colonization of the bone microenvironment disrupts the osteoblast-osteoclast balance, leading to bone lesions.

Purpose of the Study:

  • To investigate the role of osteocytes in the bone microenvironment during breast cancer metastasis.
  • To understand the cellular mechanisms underlying bone destruction in breast cancer bone metastases.

Main Methods:

  • Single-cell RNA sequencing of osteocytes from mice with bone metastases.
  • Multiplex in situ hybridization and AI-assisted analysis in mice and human patients.
  • In vitro and ex vivo organ cultures to assess breast cancer cell-induced osteocyte senescence.
  • Treatment with senolytics to clear senescent cells.

Main Results:

  • Osteocytes in established breast cancer bone metastases exhibit premature senescence and a senescence-associated secretory phenotype (SASP).
  • Senescent osteocytes express pro-osteoclastogenic genes, favoring bone resorption.
  • Breast cancer cells induce osteocyte senescence and enhance their osteoclastogenic potential.
  • Senolytic treatment reduced bone resorption and preserved bone mass in preclinical models.

Conclusions:

  • Breast cancer cells reprogram osteocytes, inducing pathological senescence and a SASP that drives bone destruction.
  • Osteocyte senescence is an initiating event in the development of lytic bone disease associated with breast cancer metastases.
  • Targeting senescent osteocytes with senolytics offers a potential therapeutic strategy to mitigate bone loss in metastatic breast cancer.