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Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

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 bone...
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Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes
11:52

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Published on: January 27, 2023

Efficient osteoclast differentiation requires local complement activation.

Zhidan Tu1, Hong Bu, James E Dennis

  • 1Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.

Blood
|August 17, 2010
PubMed
Summary
This summary is machine-generated.

Bone marrow cells locally produce complement components that activate the alternative pathway, essential for osteoclast differentiation. This process involves C3a/C5a receptors and regulates interleukin-6 (IL-6) production.

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Area of Science:

  • Immunology
  • Cell Biology
  • Bone Biology

Background:

  • Previous studies suggested bone marrow (BM)-derived C3 and its receptors are crucial for osteoclast (OC) differentiation.
  • The precise mechanisms and involvement of other complement receptors remained unclear.

Purpose of the Study:

  • To elucidate the detailed mechanism of complement involvement in osteoclast differentiation.
  • To investigate the role of C3a and C5a receptors in this process.

Main Methods:

  • Comparison of wild-type (WT) and C3(-/-) BM cells during differentiation.
  • Analysis of cytokine and complement component production.
  • Genetic and pharmaceutical abrogation of C3a/C5a receptors.
  • Supplementation with IL-6 and C3a/C5a.
  • Neutralization of IL-6.

Main Results:

  • C3(-/-) BM cells showed reduced RANKL/OPG ratios, lower MCSF and IL-6 production, and fewer OCs.
  • WT BM cells locally produced complement components activating the alternative pathway, generating C3a/C5a, crucial for OC differentiation.
  • C3aR/C5aR blockade suppressed OC generation; exogenous C3a/C5a enhanced it.
  • IL-6 supplementation rescued OC generation in C3(-/-) cells; IL-6 neutralization blocked C3a/C5a effects.

Conclusions:

  • BM cells locally activate the alternative complement pathway during OC differentiation.
  • C3aR/C5aR regulate OC differentiation, partly by modulating local IL-6 production.
  • The complement system, particularly the alternative pathway, plays a significant role in osteoclastogenesis.