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Related Concept Videos

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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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Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
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Bone contains a relatively small number of cells entrenched in a matrix of collagen fibers that provide an adherent surface for inorganic salt crystals. Both components of the matrix, organic and inorganic, contribute to the unusual properties of bone. Without collagen, bones would be brittle and shatter easily. Without mineral crystals, bones would flex and provide little support. This can be observed by an experiment: when the minerals of a bone are dissolved by soaking the bone in...
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Bones contain a relatively small number of cells entrenched in a matrix of organic and inorganic components. Although bone cells compose only a small amount of the bone volume, they are crucial to its function. Four types of cells are found within the bone tissue— osteoblasts, osteocytes, osteogenic cells, and osteoclasts.
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Endogenous Collagenases Regulate Osteoclast Fusion.

Hyo Jeong Kim1, Youngkyun Lee1,2

  • 1Department of Biochemistry, School of Dentistry, Kyungpook National University, Daegu 41940, Korea.

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|May 7, 2020
PubMed
Summary
This summary is machine-generated.

Collagenase inhibition enhances osteoclast fusion and bone resorption by regulating specific gene expression pathways. This finding offers new insights into maintaining healthy bone by controlling osteoclast activity.

Keywords:
ERKcollagenasefusionosteoclast

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Area of Science:

  • Bone Biology
  • Cellular and Molecular Biology
  • Biochemistry

Background:

  • Precise regulation of osteoclast differentiation and function is vital for bone health.
  • The specific collagenase isoforms and their roles in osteoclasts remain largely uncharacterized.

Purpose of the Study:

  • To investigate the expression and function of matrix metalloproteinase (MMP)8 and MMP13 in osteoclast precursors.
  • To elucidate the role of collagenases in osteoclast fusion and resorption.

Main Methods:

  • Confirmation of MMP8 and MMP13 expression in mouse bone marrow macrophage osteoclast precursors.
  • Analysis of mRNA and protein expression changes following receptor activator of nuclear factor κB ligand (RANKL) stimulation.
  • Assessment of osteoclast fusion and resorption activity upon MMP inhibition (siRNA or Ro 32-3555).
  • Gene expression analysis of osteoclast fusion markers (Atp6v0d2, Dcstamp) and NFATc1.
  • Investigation of the signaling pathways involved using extracellular signal regulated kinase (ERK) pathway analysis.

Main Results:

  • MMP8 and MMP13 expression was confirmed in osteoclast precursors and significantly reduced by RANKL stimulation.
  • Inhibition of MMP expression or activity augmented osteoclast fusion and resorption without altering osteoclast numbers.
  • Collagenase inhibition upregulated osteoclast fusion genes (Atp6v0d2, Dcstamp) but not NFATc1 protein.
  • Enhanced osteoclast fusion was mediated by an ERK-dependent pathway.

Conclusions:

  • This study reveals a novel regulatory role for collagenases in osteoclast fusion.
  • Inhibition of collagenase activity promotes osteoclast fusion and resorption, offering potential therapeutic targets for bone diseases.
  • The findings highlight the involvement of the ERK pathway in collagenase-mediated regulation of osteoclast fusion.