Zoledronic acid exacerbates inflammation through M1 macrophage polarization

Area of Science:

• Immunology
• Cell Biology
• Pharmacology

Background:

• Zoledronic acid (Zol) treats osteoporosis and bone metastasis but is linked to medication-related osteonecrosis of the jaw (MRONJ).
• Zol's role in inflammation, particularly its effect on macrophage polarization, requires further investigation.
• Macrophages, classified as M1 (pro-inflammatory) and M2 (anti-inflammatory), play critical roles in immune responses.

Purpose of the Study:

• To investigate the effects of Zoledronic acid (Zol) on M1 and M2 macrophage polarization in vitro.
• To elucidate the underlying molecular mechanisms of Zol-induced macrophage polarization.

Main Methods:

• Human monocytic THP-1 cells were differentiated into macrophages.
• Cells were treated with Zoledronic acid (Zol) and subsequently polarized to M1 (using LPS) or M2 (using IL-4) phenotypes.
• Gene and protein expression levels were analyzed using real-time PCR, western blotting, and ELISA.

Main Results:

• Zoledronic acid (Zol) upregulated IL-1β mRNA and protein expression in LPS-treated THP-1 cells.
• This upregulation was mediated through the activation of the NLRP3 inflammasome.
• Zol did not significantly affect the expression of IL-10, IL-1ra, or CD206 in IL-4-treated THP-1 cells.

Conclusions:

• Zoledronic acid (Zol) enhances lipopolysaccharide (LPS)-induced M1 macrophage polarization.
• This effect is dependent on the NLRP3 inflammasome pathway.
• Zol promotes an inflammatory response by increasing M1 macrophage polarization without affecting M2 polarization.