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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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Related Experiment Video

Updated: Sep 20, 2025

Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes
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THOC5 regulates human osteoclastogenesis.

Se Hwan Mun1, Brian Oh2, Min Joon Lee2

  • 1Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY 10021, USA; Research Institute of Women's Health, Sookmyung Women's University, Seoul 04310, Republic of Korea.

European Journal of Cell Biology
|June 10, 2022
PubMed
Summary
This summary is machine-generated.

THOC5 regulates osteoclast formation by interacting with c-FMS and FICD. This study reveals THOC5 as a key positive regulator in osteoclast differentiation, impacting bone resorption.

Keywords:
C-FMSM-CSFOsteoclastsTHOC5

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Bone Biology

Background:

  • Osteoclasts are crucial for bone resorption, with Macrophage Colony-Stimulating Factor (M-CSF) signaling via its receptor (c-FMS) vital for their development.
  • The THO complex member THOC5 is known to influence hematopoiesis and macrophage differentiation but its role in osteoclasts is undefined.

Purpose of the Study:

  • To elucidate the function of THOC5 in osteoclast differentiation and bone resorption.
  • To investigate the molecular mechanisms by which THOC5 influences osteoclastogenesis.

Main Methods:

  • Utilized siRNA-mediated knockdown to reduce THOC5 expression.
  • Investigated THOC5 localization and its interaction with FICD, a c-FMS cleavage product.
  • Analyzed the impact of THOC5 on key osteoclast differentiation markers like RANK, FOS, and NFATc1.

Main Results:

  • THOC5 exhibits M-CSF-dependent nucleocytoplasmic shuttling.
  • THOC5 facilitates the nuclear translocation of FICD.
  • THOC5 knockdown significantly suppressed osteoclast differentiation, affecting RANK expression and inhibiting RANKL-induced FOS and NFATc1.
  • THOC5 was identified as a positive regulator of osteoclast formation.

Conclusions:

  • THOC5 plays a critical role in osteoclast differentiation.
  • THOC5's interaction with the c-FMS pathway and its regulation of RANK signaling are key to its function in osteoclasts.
  • THOC5 represents a novel target for modulating bone resorption.