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Updated: Dec 10, 2025
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Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes
Published on: January 27, 2023
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Human dendritic cell-derived osteoclasts with high bone resorption capacity and T cell stimulation ability
Manabu Narisawa1, Satoshi Kubo1, Yosuke Okada1
1The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka, Japan.
Bone
|September 1, 2020
Summary
Dendritic cell-derived osteoclasts (DC-OC) in humans exhibit enhanced bone resorption and T-cell stimulation. These DC-OC are found in rheumatoid arthritis patients, contributing to bone destruction and inflammation.
Area of Science:
- Immunology
- Cell Biology
- Rheumatology
Background:
- Osteoclasts are crucial for bone remodeling, typically derived from monocytes.
- A subset of osteoclasts, dendritic cell-derived osteoclasts (DC-OC), has been identified in mice models of arthritis.
- The role and characteristics of human DC-OC remain largely uncharacterized.
Purpose of the Study:
- To investigate the function and pathological significance of human dendritic cell-derived osteoclasts (DC-OC).
- To compare the bone resorption and antigen-presenting capabilities of DC-OC with monocyte-derived osteoclasts (Mo-OC).
- To examine the presence and characteristics of DC-OC in patients with rheumatoid arthritis.
Main Methods:
- In vitro differentiation of DC-OC from human monocyte-derived dendritic cells (DC) using M-CSF and RANKL.
- Pit formation assays to assess bone resorption activity.
- Co-culture experiments with T-cells to evaluate antigen-presenting function.
- Analysis of synovial tissue samples from rheumatoid arthritis (RA) and osteoarthritis (OA) patients.
Main Results:
- Human DC-OC are multinucleated, cathepsin K and TRAP-positive, and exhibit superior bone resorption compared to Mo-OC.
- DC-OC retain CD11c expression and costimulatory molecules, effectively stimulating T-cell proliferation.
- Abatacept reduced DC-OC T-cell stimulating activity but did not inhibit DC-OC differentiation.
- TRAP-positive and CD86-positive DC-OC were identified in RA synovial tissues, but not in OA tissues.
Conclusions:
- Human DC-OC possess potent osteolytic and T-cell stimulating functions.
- The presence of DC-OC in rheumatoid arthritis synovial membranes suggests their contribution to joint inflammation and bone destruction.
- DC-OC represent a potential therapeutic target in inflammatory bone diseases like rheumatoid arthritis.
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