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An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function
Julia F Charles1, Lih-Yun Hsu, Erene C Niemi
1Department of Medicine, Division of Rheumatology, UCSF, San Francisco, California, USA. jfcharles@partners.org
The Journal of Clinical Investigation
|November 2, 2012
Summary
Researchers identified a novel myeloid precursor population in bone marrow with osteoclast-forming and T cell-suppressing abilities. These precursors expand in inflammatory arthritis and may offer new therapeutic targets for rheumatoid arthritis (RA).
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Rheumatoid arthritis (RA) involves increased osteoclast bone resorption, leading to joint erosion and osteoporosis.
- The specific in vivo osteoclast precursor (OCP) population and its role in RA pathogenesis are not fully understood.
Purpose of the Study:
- To identify and characterize a novel osteoclast precursor (OCP) population in vivo.
- To investigate the role of this OCP population in inflammatory arthritis and T cell regulation.
Main Methods:
- Identification of a CD11b(-/lo)Ly6C(hi) bone marrow (BM) population with OCP activity.
- In vitro and in vivo assays to assess osteoclast differentiation and T cell suppression.
- Analysis of OCP expansion in inflammatory arthritis mouse models.
Main Results:
- A novel BM myeloid precursor population (CD11b(-/lo)Ly6C(hi)) exhibiting OCP activity was identified.
- These OCPs display mixed M1/M2 monocyte features and expand during inflammatory arthritis.
- OCPs suppressed T cell proliferation in vitro via nitric oxide (NO) production, similar to monocytic myeloid-derived suppressor cells (M-MDSCs).
Conclusions:
- A BM myeloid precursor population with both osteoclastic and T cell-suppressive functions has been identified and is expanded in inflammatory arthritis.
- Targeting OCP development into bone-resorbing cells could simultaneously address bone loss and inflammation in RA.
- This OCP population represents a potential therapeutic target for rheumatoid arthritis.
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