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Updated: Nov 16, 2025

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A Simple Pit Assay Protocol to Visualize and Quantify Osteoclastic Resorption In Vitro
Published on: June 16, 2022
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Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption.
Michelle M McDonald1, Weng Hua Khoo1, Pei Ying Ng2
1Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia.
Cell
|February 26, 2021
Summary
Osteoclasts, the bone-resorbing cells, can recycle into new cells called osteomorphs. This discovery offers potential new targets for treating bone diseases.
Area of Science:
- Cell Biology
- Skeletal Biology
- Osteoclast Biology
Background:
- Osteoclasts are multinucleated cells responsible for bone resorption.
- They are derived from monocyte/macrophage precursors.
- Osteoclasts were previously thought to undergo apoptosis after bone resorption.
Purpose of the Study:
- To investigate the fate of osteoclasts after bone resorption.
- To identify alternative cell fates beyond apoptosis.
- To explore the potential therapeutic targets for skeletal diseases.
Main Methods:
- Intravital imaging to observe osteoclast behavior in vivo.
- RANKL stimulation and inhibition experiments.
- Single-cell RNA sequencing to analyze gene expression in daughter cells.
- Genetic analysis of human orthologs.
Main Results:
- Osteoclasts undergo fission into daughter cells named osteomorphs.
- RANKL inhibition prevents osteoclast recycling and causes osteomorph accumulation.
- Osteomorphs are transcriptionally distinct from osteoclasts and macrophages.
- Osteomorph genes are linked to skeletal disorders and bone mineral density.
Conclusions:
- Osteoclasts have an alternative recycling pathway via osteomorphs.
- Osteomorphs play a role in regulating bone resorption.
- Osteomorphs represent a potential therapeutic target for skeletal diseases.
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