Zoledronic acid promotes TLR-4–mediated M1 macrophage polarization in bisphosphonate-related osteonecrosis of the jaw

What is it about?

Bisphosphonate-related osteonecrosis of the Jaw(BRONJ) is a detrimental side effect due to the bisphosphonates administration, which presents an unhealed tooth extraction socket for more than 8 weeks. Here, we use BRONJ-like disease mice models to investigate the possible pathogenesis of BRONJ. By utilizing TLR-4-/- mice, we found that BRONJ development was ameliorated in TLR-4-/- mice. Furthermore, we found that the pro-inflammatory macrophages were also reduced in TLR-4-/- mice. Next, the administration of TLR-4 inhibitor reduced the BRONJ incidence rate in wild-type mice. Taken together, our findings suggest that TLR-4-mediated pro-inflammatory macrophage polarization participates in the pathogenesis of BRONJ in mice, and TLR-4 may be a potential target for prevention and therapeutic treatment of BRONJ.

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