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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
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Updated: May 20, 2025

Osteoclast Derivation from Mouse Bone Marrow
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Developmental Endothelial Locus-1 Promotes Osteoclast Differentiation and Activation.

Kentaro Imamura1,2, Keita Tachi3, Tadahiro Takayama4

  • 1Department of Periodontology, Tokyo Dental College, Chiyoda-ku, Tokyo 101-0061, Japan.

International Journal of Molecular Sciences
|March 27, 2025
PubMed
Summary

Developmental endothelial locus-1 (DEL-1) surprisingly promotes osteoclast formation, challenging its known anti-inflammatory role. This finding suggests DEL-1

Keywords:
DEL-1bone metabolismosteoclastsosteoporosis

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Area of Science:

  • Skeletal Biology
  • Cell Biology
  • Immunology

Background:

  • Developmental endothelial locus-1 (DEL-1) is traditionally recognized for anti-inflammatory effects.
  • Its role in osteoclastogenesis, the process of bone-resorbing cell formation, has been unclear.

Purpose of the Study:

  • To investigate the role of DEL-1 in osteoclast differentiation and activity.
  • To challenge the established paradigm of DEL-1's function in bone metabolism.

Main Methods:

  • Examined Del-1 mRNA expression in RAW264.7 cells and bone marrow-derived macrophages (BMMs) during osteoclastogenesis.
  • Assessed the impact of recombinant DEL-1 on osteoclast differentiation.
  • Utilized RNA interference to silence Del-1 in RAW264.7 cells.
  • Analyzed Del-1 expression in BMMs from ovariectomized and control mice.

Main Results:

  • Del-1 mRNA levels significantly increased upon stimulation with receptor activator of nuclear factor κB ligand.
  • Recombinant DEL-1 promoted osteoclast differentiation in a dose-dependent manner.
  • Del-1 expression was elevated in BMMs from ovariectomized mice.
  • Silencing Del-1 markedly reduced osteoclast formation.

Conclusions:

  • DEL-1 actively promotes osteoclastogenesis, contrary to previous assumptions.
  • This newly identified role suggests DEL-1's involvement in bone metabolism disorders like osteoporosis.
  • DEL-1 represents a potential therapeutic target for skeletal homeostasis regulation.