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Updated: Jun 3, 2026
11:52
Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes
Published on: January 27, 2023
Nucleosides accelerate inflammatory osteolysis, acting as distinct innate immune activators
George Pan1, Rui Zheng, Pingar Yang
1Department of Pediatrics, Emory University, Atlanta, GA 30322, USA. zpan2@emory.edu
Summary
Nucleosides activate innate immunity, accelerating inflammatory bone destruction and osteoclast formation in autoimmune conditions. These findings reveal new mechanisms in osteoarthritis pathogenesis.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- The innate immune system contributes to inflammatory bone destruction, but other mediators beyond cytokines are implicated in osteolysis.
- Previous research indicated nucleosides promote osteoclastogenesis and bone resorption with receptor activator for nuclear factor κB ligand (RANKL).
Purpose of the Study:
- To investigate the role of nucleosides and their analogues in accelerating bone destruction in autoimmune models.
- To explore the mechanisms underlying nucleoside-enhanced osteoclastogenesis, including the involvement of TREM and inflammasomes.
Main Methods:
- Utilizing mouse models immunized with collagen II (CII) alone or with complete Freund's adjuvant (CFA).
- Assessing bone destruction, osteoclast accumulation, and the expression of TREM and inflammasome components.
Main Results:
- Selected nucleosides and analogues accelerated bone destruction in CII-immunized mice and enhanced erosion in CII + CFA-immunized mice.
- Abundant osteoclasts were observed in affected joints, indicating accelerated osteoclast formation.
- Nucleosides acted as innate immune activators, synergizing with existing inflammatory stimuli to promote osteolysis.
Conclusions:
- Nucleosides function as distinct innate immune activators that synergistically enhance inflammatory osteolysis.
- These findings offer novel insights into the pathogenesis and mechanisms of bone destruction in inflammatory autoimmune diseases like osteoarthritis.
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