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Osteoclasts in Bone Remodeling01:31

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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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Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
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A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
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Related Experiment Video

Updated: Jun 8, 2025

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
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Autophagy Regulator Rufy 4 Promotes Osteoclastic Bone Resorption by Orchestrating Cytoskeletal Organization via Its

Eiko Sakai1, Minoru Saito1,2, Yu Koyanagi1,3

  • 1Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.

Cells
|November 8, 2024
PubMed
Summary
This summary is machine-generated.

Rufy4 protein regulates osteoclast activity, impacting bone resorption. Silencing Rufy4 enhances differentiation but reduces bone breakdown, while overexpression has opposite effects, highlighting its therapeutic potential for bone disorders.

Keywords:
RUN and FYVE domain-containing protein familyRufy4autophagybone resorptioncathepsin Kcytoskeleton organizationintracellular traffickingosteoclastsiRNA

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Bone Biology

Background:

  • Rufy4 (RUN and FYVE domain-containing protein 4) is involved in cellular processes.
  • Its specific role in osteoclast-mediated bone resorption is not well understood.

Purpose of the Study:

  • To investigate the expression and function of Rufy4 in osteoclasts.
  • To elucidate Rufy4's role in osteoclast differentiation and bone resorption.

Main Methods:

  • Used small interfering RNA (siRNA) for Rufy4 knockdown in osteoclasts.
  • Employed gene overexpression systems for wild-type and variant Rufy4.
  • Assessed osteoclast differentiation, cathepsin K levels, cytoskeletal structures, and bone resorption activity.

Main Results:

  • Rufy4 expression increased during osteoclast differentiation.
  • Rufy4 knockdown enhanced differentiation and axial protrusions but suppressed bone resorption.
  • Overexpression of Rufy4 or its RUN domain-lacking variant altered differentiation, podosome formation, and bone resorption.
  • Rufy4's RUN domain is critical for regulating cytoskeletal organization.

Conclusions:

  • Rufy4 plays a crucial role in osteoclast differentiation and bone resorption.
  • Rufy4 regulates these processes by influencing cytoskeletal organization via its RUN domain.
  • Rufy4 represents a potential therapeutic target for bone diseases with excessive bone resorption.